The Val158Met COMT polymorphism is a modifier of the age at onset in Parkinson's disease with a sexual dimorphism
Identifieur interne : 000770 ( Pmc/Curation ); précédent : 000769; suivant : 000771The Val158Met COMT polymorphism is a modifier of the age at onset in Parkinson's disease with a sexual dimorphism
Auteurs : Stephan Klebe [France, Allemagne] ; Jean-Louis Golmard [France] ; Michael A. Nalls [États-Unis] ; Mohamad Saad [France] ; Andrew B. Singleton [États-Unis] ; Jose M. Bras [Royaume-Uni] ; John Hardy [Royaume-Uni] ; Javier Simon-Sanchez [États-Unis, Pays-Bas] ; Peter Heutink [Pays-Bas] ; Gregor Kuhlenb Umer [Allemagne] ; Rim Charfi [France, Tunisie] ; Christine Klein [Allemagne] ; Johann Hagenah [Allemagne] ; Thomas Gasser [Allemagne] ; Isabel Wurster [Allemagne] ; Suzanne Lesage [France] ; Delia Lorenz [Allemagne] ; Günther Deuschl [Allemagne] ; Franck Durif [France] ; Pierre Pollak [France] ; Philippe Damier [France] ; François Tison [France] ; Alexandra Durr [France] ; Philippe Amouyel [France] ; Jean-Charles Lambert [France] ; Christophe Tzourio [France] ; Cécilia Maubaret [France] ; Fanny Charbonnier-Beaupel [France] ; Khadija Tahiri [France] ; Marie Vidailhet [France] ; Maria Martinez [France] ; Alexis Brice [France] ; Jean-Christophe Corvol [France]Source :
- Journal of Neurology, Neurosurgery, and Psychiatry [ 0022-3050 ] ; 2013.
Abstract
The catechol-O-methyltranferase (COMT) is one of the main enzymes that metabolise dopamine in the brain. The Val158Met polymorphism in the
Url:
DOI: 10.1136/jnnp-2012-304475
PubMed: 23408064
PubMed Central: 3646288
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Nalls</name><affiliation wicri:level="1"><nlm:aff id="af9"><addr-line>Laboratory of Neurogenetics</addr-line>,<institution>National Institute on Aging, National Institutes of Health</institution>,<addr-line>Bethesda Maryland</addr-line>,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Saad, Mohamad" sort="Saad, Mohamad" uniqKey="Saad M" first="Mohamad" last="Saad">Mohamad Saad</name><affiliation wicri:level="1"><nlm:aff id="af10"><institution>INSERM U1043, CPTP</institution>,<addr-line>Toulouse</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af11"><institution>Paul Sabatier University</institution>,<addr-line>Toulouse</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Singleton, Andrew B" sort="Singleton, Andrew B" uniqKey="Singleton A" first="Andrew B" last="Singleton">Andrew B. Singleton</name><affiliation wicri:level="1"><nlm:aff id="af9"><addr-line>Laboratory of Neurogenetics</addr-line>,<institution>National Institute on Aging, National Institutes of Health</institution>,<addr-line>Bethesda Maryland</addr-line>,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bras, Jose M" sort="Bras, Jose M" uniqKey="Bras J" first="Jose M" last="Bras">Jose M. Bras</name><affiliation wicri:level="1"><nlm:aff id="af12"><addr-line>Department of Molecular Neuroscience</addr-line>,<institution>UCL Institute of Neurology</institution>,<addr-line>London</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hardy, John" sort="Hardy, John" uniqKey="Hardy J" first="John" last="Hardy">John Hardy</name><affiliation wicri:level="1"><nlm:aff id="af12"><addr-line>Department of Molecular Neuroscience</addr-line>,<institution>UCL Institute of Neurology</institution>,<addr-line>London</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Simon Sanchez, Javier" sort="Simon Sanchez, Javier" uniqKey="Simon Sanchez J" first="Javier" last="Simon-Sanchez">Javier Simon-Sanchez</name><affiliation wicri:level="1"><nlm:aff id="af9"><addr-line>Laboratory of Neurogenetics</addr-line>,<institution>National Institute on Aging, National Institutes of Health</institution>,<addr-line>Bethesda Maryland</addr-line>,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af13"><addr-line>Department of Clinical Genetics Section of Medical Genomics</addr-line>,<institution>VU Medical Center</institution>,<addr-line>Amsterdam</addr-line>,<country>Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Heutink, Peter" sort="Heutink, Peter" uniqKey="Heutink P" first="Peter" last="Heutink">Peter Heutink</name><affiliation wicri:level="1"><nlm:aff id="af13"><addr-line>Department of Clinical Genetics Section of Medical Genomics</addr-line>,<institution>VU Medical Center</institution>,<addr-line>Amsterdam</addr-line>,<country>Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kuhlenb Umer, Gregor" sort="Kuhlenb Umer, Gregor" uniqKey="Kuhlenb Umer G" first="Gregor" last="Kuhlenb Umer">Gregor Kuhlenb Umer</name><affiliation wicri:level="1"><nlm:aff id="af14"><institution>Institute of Experimental Medicine, Christian-Albrechts University</institution>,<addr-line>Kiel</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Charfi, Rim" sort="Charfi, Rim" uniqKey="Charfi R" first="Rim" last="Charfi">Rim Charfi</name><affiliation wicri:level="1"><nlm:aff id="af15"><addr-line>Assistance Publique Hôpitaux de Paris, Department of Pharmacology</addr-line>,<institution>Hôpital de la Pitié-Salpêtrière</institution>,<addr-line>Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af16"><addr-line>Faculté de Médecine de Tunis</addr-line>,<institution>Université de Tunis El Manar</institution>,<institution>Centre National de Pharmacovigilance de Tunis, Service de Pharmacologie Clinique</institution>,<addr-line>Tunis</addr-line>,<country>Tunisia</country></nlm:aff><country xml:lang="fr">Tunisie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Klein, Christine" sort="Klein, Christine" uniqKey="Klein C" first="Christine" last="Klein">Christine Klein</name><affiliation wicri:level="1"><nlm:aff id="af17"><addr-line>Institute of Neurogenetics</addr-line>,<institution>University of Lübeck</institution>,<addr-line>Lübeck</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hagenah, Johann" sort="Hagenah, Johann" uniqKey="Hagenah J" first="Johann" last="Hagenah">Johann Hagenah</name><affiliation wicri:level="1"><nlm:aff id="af17"><addr-line>Institute of Neurogenetics</addr-line>,<institution>University of Lübeck</institution>,<addr-line>Lübeck</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Gasser, Thomas" sort="Gasser, Thomas" uniqKey="Gasser T" first="Thomas" last="Gasser">Thomas Gasser</name><affiliation wicri:level="1"><nlm:aff id="af18"><addr-line>Department of Neurodegenerative Diseases</addr-line>,<institution>Hertie-Institute for Clinical Brain Research, University of Tübingen</institution>,<addr-line>Tübingen</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af19"><addr-line>Department of Neurodegenerative Diseases</addr-line>,<institution>German Center for Neurodegenerative Diseases (DZNE)</institution>,<addr-line>Tübingen</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wurster, Isabel" sort="Wurster, Isabel" uniqKey="Wurster I" first="Isabel" last="Wurster">Isabel Wurster</name><affiliation wicri:level="1"><nlm:aff id="af18"><addr-line>Department of Neurodegenerative Diseases</addr-line>,<institution>Hertie-Institute for Clinical Brain Research, University of Tübingen</institution>,<addr-line>Tübingen</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af19"><addr-line>Department of Neurodegenerative Diseases</addr-line>,<institution>German Center for Neurodegenerative Diseases (DZNE)</institution>,<addr-line>Tübingen</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lesage, Suzanne" sort="Lesage, Suzanne" uniqKey="Lesage S" first="Suzanne" last="Lesage">Suzanne Lesage</name><affiliation wicri:level="1"><nlm:aff id="af1"><institution>INSERM, UMR_S975</institution>,<addr-line>CR-ICM, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af2"><institution>UPMC University Paris 06, UMR_S975</institution>,<addr-line>CR-ICM, Pitié-Salpêtrière Hospital, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af3"><institution>CNRS UMR 7225</institution>,<addr-line>CR-ICM, Pitié-Salpêtrière Hospital, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lorenz, Delia" sort="Lorenz, Delia" uniqKey="Lorenz D" first="Delia" last="Lorenz">Delia Lorenz</name><affiliation wicri:level="1"><nlm:aff id="af20"><addr-line>Department of Neurology</addr-line>,<institution>UKS-H, Campus Kiel; Christian-Albrechts-University</institution>,<addr-line>Kiel</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Deuschl, Gunther" sort="Deuschl, Gunther" uniqKey="Deuschl G" first="Günther" last="Deuschl">Günther Deuschl</name><affiliation wicri:level="1"><nlm:aff id="af20"><addr-line>Department of Neurology</addr-line>,<institution>UKS-H, Campus Kiel; Christian-Albrechts-University</institution>,<addr-line>Kiel</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Durif, Franck" sort="Durif, Franck" uniqKey="Durif F" first="Franck" last="Durif">Franck Durif</name><affiliation wicri:level="1"><nlm:aff id="af21"><addr-line>Hôpital Gabriel Montpied, CHU de Grenoble, Department of Neurology</addr-line>,<addr-line>Clermont-Ferrand</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Pollak, Pierre" sort="Pollak, Pierre" uniqKey="Pollak P" first="Pierre" last="Pollak">Pierre Pollak</name><affiliation wicri:level="1"><nlm:aff id="af22"><addr-line>CHU de Grenoble, Department of Neurology</addr-line>,<addr-line>Grenoble</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Damier, Philippe" sort="Damier, Philippe" uniqKey="Damier P" first="Philippe" last="Damier">Philippe Damier</name><affiliation wicri:level="1"><nlm:aff id="af23"><addr-line>CHU de Nantes, Centre d'Investigation Clinique</addr-line>,<addr-line>Nantes</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Tison, Francois" sort="Tison, Francois" uniqKey="Tison F" first="François" last="Tison">François Tison</name><affiliation wicri:level="1"><nlm:aff id="af24"><addr-line>Hôpital Haut-Lévêque, Department of Neurology</addr-line>,<addr-line>Pessac</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Durr, Alexandra" sort="Durr, Alexandra" uniqKey="Durr A" first="Alexandra" last="Durr">Alexandra Durr</name><affiliation wicri:level="1"><nlm:aff id="af1"><institution>INSERM, UMR_S975</institution>,<addr-line>CR-ICM, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af2"><institution>UPMC University Paris 06, UMR_S975</institution>,<addr-line>CR-ICM, Pitié-Salpêtrière Hospital, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af3"><institution>CNRS UMR 7225</institution>,<addr-line>CR-ICM, Pitié-Salpêtrière Hospital, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af4"><addr-line>Assitance Publique Hôpitaux de Paris, Département de Génétique et Cytogénétique</addr-line>,<institution>Hôpital de la Pitié-Salpêtrière</institution>,<addr-line>Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Amouyel, Philippe" sort="Amouyel, Philippe" uniqKey="Amouyel P" first="Philippe" last="Amouyel">Philippe Amouyel</name><affiliation wicri:level="1"><nlm:aff id="af25"><institution>INSERM, U744</institution>,<addr-line>Lille</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af26"><institution>Institut Pasteur de Lille</institution>,<addr-line>Lille</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af27"><institution>Université Lille-Nord de France</institution>,<addr-line>Lille</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lambert, Jean Charles" sort="Lambert, Jean Charles" uniqKey="Lambert J" first="Jean-Charles" last="Lambert">Jean-Charles Lambert</name><affiliation wicri:level="1"><nlm:aff id="af25"><institution>INSERM, U744</institution>,<addr-line>Lille</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af26"><institution>Institut Pasteur de Lille</institution>,<addr-line>Lille</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af27"><institution>Université Lille-Nord de France</institution>,<addr-line>Lille</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Tzourio, Christophe" sort="Tzourio, Christophe" uniqKey="Tzourio C" first="Christophe" last="Tzourio">Christophe Tzourio</name><affiliation wicri:level="1"><nlm:aff id="af28"><institution>Université Pierre et Marie Curie—Paris 6, CNRS 7225 CRICM, ER4-UPMC Modélisation en recherche clinique, Hôpital Pitié-Salpêtrière</institution>,<addr-line>Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation><nlm:aff id="af29"><addr-line>INSERM UMR_S708, Neuroépidémiologie</addr-line>,<institution>Paris, France</institution></nlm:aff></affiliation></author><author><name sortKey="Maubaret, Cecilia" sort="Maubaret, Cecilia" uniqKey="Maubaret C" first="Cécilia" last="Maubaret">Cécilia Maubaret</name><affiliation wicri:level="1"><nlm:aff id="af30"><institution>INSERM U897, Université Bordeaux Ségalen</institution>,<addr-line>Bordeaux</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Charbonnier Beaupel, Fanny" sort="Charbonnier Beaupel, Fanny" uniqKey="Charbonnier Beaupel F" first="Fanny" last="Charbonnier-Beaupel">Fanny Charbonnier-Beaupel</name><affiliation wicri:level="1"><nlm:aff id="af1"><institution>INSERM, UMR_S975</institution>,<addr-line>CR-ICM, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af2"><institution>UPMC University Paris 06, UMR_S975</institution>,<addr-line>CR-ICM, Pitié-Salpêtrière Hospital, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af3"><institution>CNRS UMR 7225</institution>,<addr-line>CR-ICM, Pitié-Salpêtrière Hospital, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Tahiri, Khadija" sort="Tahiri, Khadija" uniqKey="Tahiri K" first="Khadija" last="Tahiri">Khadija Tahiri</name><affiliation wicri:level="1"><nlm:aff id="af1"><institution>INSERM, UMR_S975</institution>,<addr-line>CR-ICM, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af2"><institution>UPMC University Paris 06, UMR_S975</institution>,<addr-line>CR-ICM, Pitié-Salpêtrière Hospital, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af3"><institution>CNRS UMR 7225</institution>,<addr-line>CR-ICM, Pitié-Salpêtrière Hospital, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Vidailhet, Marie" sort="Vidailhet, Marie" uniqKey="Vidailhet M" first="Marie" last="Vidailhet">Marie Vidailhet</name><affiliation wicri:level="1"><nlm:aff id="af2"><institution>UPMC University Paris 06, UMR_S975</institution>,<addr-line>CR-ICM, Pitié-Salpêtrière Hospital, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af3"><institution>CNRS UMR 7225</institution>,<addr-line>CR-ICM, Pitié-Salpêtrière Hospital, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af6"><addr-line>Assistance Publique Hôpitaux de Paris, Department of Neurology</addr-line>,<institution>Hôpital de la Pitié-Salpêtrière</institution>,<addr-line>Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af31"><addr-line>“Movement Disorders and Basal Ganglia: Pathophysiology and experimental Therapeutics”</addr-line>,<institution>INSERM, UMR_S975</institution>,<addr-line>Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Martinez, Maria" sort="Martinez, Maria" uniqKey="Martinez M" first="Maria" last="Martinez">Maria Martinez</name><affiliation wicri:level="1"><nlm:aff id="af10"><institution>INSERM U1043, CPTP</institution>,<addr-line>Toulouse</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af11"><institution>Paul Sabatier University</institution>,<addr-line>Toulouse</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Brice, Alexis" sort="Brice, Alexis" uniqKey="Brice A" first="Alexis" last="Brice">Alexis Brice</name><affiliation wicri:level="1"><nlm:aff id="af1"><institution>INSERM, UMR_S975</institution>,<addr-line>CR-ICM, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af2"><institution>UPMC University Paris 06, UMR_S975</institution>,<addr-line>CR-ICM, Pitié-Salpêtrière Hospital, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af3"><institution>CNRS UMR 7225</institution>,<addr-line>CR-ICM, Pitié-Salpêtrière Hospital, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af4"><addr-line>Assitance Publique Hôpitaux de Paris, Département de Génétique et Cytogénétique</addr-line>,<institution>Hôpital de la Pitié-Salpêtrière</institution>,<addr-line>Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af6"><addr-line>Assistance Publique Hôpitaux de Paris, Department of Neurology</addr-line>,<institution>Hôpital de la Pitié-Salpêtrière</institution>,<addr-line>Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Corvol, Jean Christophe" sort="Corvol, Jean Christophe" uniqKey="Corvol J" first="Jean-Christophe" last="Corvol">Jean-Christophe Corvol</name><affiliation wicri:level="1"><nlm:aff id="af1"><institution>INSERM, UMR_S975</institution>,<addr-line>CR-ICM, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af2"><institution>UPMC University Paris 06, UMR_S975</institution>,<addr-line>CR-ICM, Pitié-Salpêtrière Hospital, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af3"><institution>CNRS UMR 7225</institution>,<addr-line>CR-ICM, Pitié-Salpêtrière Hospital, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af5"><institution>INSERM, CIC-9503, Hôpital de la Pitié-Salpêtrière</institution>,<addr-line>Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af15"><addr-line>Assistance Publique Hôpitaux de Paris, Department of Pharmacology</addr-line>,<institution>Hôpital de la Pitié-Salpêtrière</institution>,<addr-line>Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23408064</idno><idno type="pmc">3646288</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646288</idno><idno type="RBID">PMC:3646288</idno><idno type="doi">10.1136/jnnp-2012-304475</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">000773</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000773</idno><idno type="wicri:Area/Pmc/Curation">000770</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000770</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">The Val158Met COMT polymorphism is a modifier of the age at onset in Parkinson's disease with a sexual dimorphism</title><author><name sortKey="Klebe, Stephan" sort="Klebe, Stephan" uniqKey="Klebe S" first="Stephan" last="Klebe">Stephan Klebe</name><affiliation wicri:level="1"><nlm:aff id="af1"><institution>INSERM, UMR_S975</institution>,<addr-line>CR-ICM, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af2"><institution>UPMC University Paris 06, UMR_S975</institution>,<addr-line>CR-ICM, Pitié-Salpêtrière Hospital, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af3"><institution>CNRS UMR 7225</institution>,<addr-line>CR-ICM, Pitié-Salpêtrière Hospital, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af4"><addr-line>Assitance Publique Hôpitaux de Paris, Département de Génétique et Cytogénétique</addr-line>,<institution>Hôpital de la Pitié-Salpêtrière</institution>,<addr-line>Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af5"><institution>INSERM, CIC-9503, Hôpital de la Pitié-Salpêtrière</institution>,<addr-line>Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af6"><addr-line>Assistance Publique Hôpitaux de Paris, Department of Neurology</addr-line>,<institution>Hôpital de la Pitié-Salpêtrière</institution>,<addr-line>Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af7"><addr-line>Department of Neurology</addr-line>,<institution>University Hospital Würzburg</institution>,<addr-line>Würzburg</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Golmard, Jean Louis" sort="Golmard, Jean Louis" uniqKey="Golmard J" first="Jean-Louis" last="Golmard">Jean-Louis Golmard</name><affiliation wicri:level="1"><nlm:aff id="af8"><addr-line>Assistance Publique Hôpitaux de Paris, Department of Biostatistics</addr-line>,<institution>Hôpital de la Pitié-Salpêtrière</institution>,<addr-line>Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Nalls, Michael A" sort="Nalls, Michael A" uniqKey="Nalls M" first="Michael A" last="Nalls">Michael A. Nalls</name><affiliation wicri:level="1"><nlm:aff id="af9"><addr-line>Laboratory of Neurogenetics</addr-line>,<institution>National Institute on Aging, National Institutes of Health</institution>,<addr-line>Bethesda Maryland</addr-line>,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Saad, Mohamad" sort="Saad, Mohamad" uniqKey="Saad M" first="Mohamad" last="Saad">Mohamad Saad</name><affiliation wicri:level="1"><nlm:aff id="af10"><institution>INSERM U1043, CPTP</institution>,<addr-line>Toulouse</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af11"><institution>Paul Sabatier University</institution>,<addr-line>Toulouse</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Singleton, Andrew B" sort="Singleton, Andrew B" uniqKey="Singleton A" first="Andrew B" last="Singleton">Andrew B. Singleton</name><affiliation wicri:level="1"><nlm:aff id="af9"><addr-line>Laboratory of Neurogenetics</addr-line>,<institution>National Institute on Aging, National Institutes of Health</institution>,<addr-line>Bethesda Maryland</addr-line>,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bras, Jose M" sort="Bras, Jose M" uniqKey="Bras J" first="Jose M" last="Bras">Jose M. Bras</name><affiliation wicri:level="1"><nlm:aff id="af12"><addr-line>Department of Molecular Neuroscience</addr-line>,<institution>UCL Institute of Neurology</institution>,<addr-line>London</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hardy, John" sort="Hardy, John" uniqKey="Hardy J" first="John" last="Hardy">John Hardy</name><affiliation wicri:level="1"><nlm:aff id="af12"><addr-line>Department of Molecular Neuroscience</addr-line>,<institution>UCL Institute of Neurology</institution>,<addr-line>London</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Simon Sanchez, Javier" sort="Simon Sanchez, Javier" uniqKey="Simon Sanchez J" first="Javier" last="Simon-Sanchez">Javier Simon-Sanchez</name><affiliation wicri:level="1"><nlm:aff id="af9"><addr-line>Laboratory of Neurogenetics</addr-line>,<institution>National Institute on Aging, National Institutes of Health</institution>,<addr-line>Bethesda Maryland</addr-line>,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af13"><addr-line>Department of Clinical Genetics Section of Medical Genomics</addr-line>,<institution>VU Medical Center</institution>,<addr-line>Amsterdam</addr-line>,<country>Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Heutink, Peter" sort="Heutink, Peter" uniqKey="Heutink P" first="Peter" last="Heutink">Peter Heutink</name><affiliation wicri:level="1"><nlm:aff id="af13"><addr-line>Department of Clinical Genetics Section of Medical Genomics</addr-line>,<institution>VU Medical Center</institution>,<addr-line>Amsterdam</addr-line>,<country>Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kuhlenb Umer, Gregor" sort="Kuhlenb Umer, Gregor" uniqKey="Kuhlenb Umer G" first="Gregor" last="Kuhlenb Umer">Gregor Kuhlenb Umer</name><affiliation wicri:level="1"><nlm:aff id="af14"><institution>Institute of Experimental Medicine, Christian-Albrechts University</institution>,<addr-line>Kiel</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Charfi, Rim" sort="Charfi, Rim" uniqKey="Charfi R" first="Rim" last="Charfi">Rim Charfi</name><affiliation wicri:level="1"><nlm:aff id="af15"><addr-line>Assistance Publique Hôpitaux de Paris, Department of Pharmacology</addr-line>,<institution>Hôpital de la Pitié-Salpêtrière</institution>,<addr-line>Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af16"><addr-line>Faculté de Médecine de Tunis</addr-line>,<institution>Université de Tunis El Manar</institution>,<institution>Centre National de Pharmacovigilance de Tunis, Service de Pharmacologie Clinique</institution>,<addr-line>Tunis</addr-line>,<country>Tunisia</country></nlm:aff><country xml:lang="fr">Tunisie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Klein, Christine" sort="Klein, Christine" uniqKey="Klein C" first="Christine" last="Klein">Christine Klein</name><affiliation wicri:level="1"><nlm:aff id="af17"><addr-line>Institute of Neurogenetics</addr-line>,<institution>University of Lübeck</institution>,<addr-line>Lübeck</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hagenah, Johann" sort="Hagenah, Johann" uniqKey="Hagenah J" first="Johann" last="Hagenah">Johann Hagenah</name><affiliation wicri:level="1"><nlm:aff id="af17"><addr-line>Institute of Neurogenetics</addr-line>,<institution>University of Lübeck</institution>,<addr-line>Lübeck</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Gasser, Thomas" sort="Gasser, Thomas" uniqKey="Gasser T" first="Thomas" last="Gasser">Thomas Gasser</name><affiliation wicri:level="1"><nlm:aff id="af18"><addr-line>Department of Neurodegenerative Diseases</addr-line>,<institution>Hertie-Institute for Clinical Brain Research, University of Tübingen</institution>,<addr-line>Tübingen</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af19"><addr-line>Department of Neurodegenerative Diseases</addr-line>,<institution>German Center for Neurodegenerative Diseases (DZNE)</institution>,<addr-line>Tübingen</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wurster, Isabel" sort="Wurster, Isabel" uniqKey="Wurster I" first="Isabel" last="Wurster">Isabel Wurster</name><affiliation wicri:level="1"><nlm:aff id="af18"><addr-line>Department of Neurodegenerative Diseases</addr-line>,<institution>Hertie-Institute for Clinical Brain Research, University of Tübingen</institution>,<addr-line>Tübingen</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af19"><addr-line>Department of Neurodegenerative Diseases</addr-line>,<institution>German Center for Neurodegenerative Diseases (DZNE)</institution>,<addr-line>Tübingen</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lesage, Suzanne" sort="Lesage, Suzanne" uniqKey="Lesage S" first="Suzanne" last="Lesage">Suzanne Lesage</name><affiliation wicri:level="1"><nlm:aff id="af1"><institution>INSERM, UMR_S975</institution>,<addr-line>CR-ICM, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af2"><institution>UPMC University Paris 06, UMR_S975</institution>,<addr-line>CR-ICM, Pitié-Salpêtrière Hospital, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af3"><institution>CNRS UMR 7225</institution>,<addr-line>CR-ICM, Pitié-Salpêtrière Hospital, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lorenz, Delia" sort="Lorenz, Delia" uniqKey="Lorenz D" first="Delia" last="Lorenz">Delia Lorenz</name><affiliation wicri:level="1"><nlm:aff id="af20"><addr-line>Department of Neurology</addr-line>,<institution>UKS-H, Campus Kiel; Christian-Albrechts-University</institution>,<addr-line>Kiel</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Deuschl, Gunther" sort="Deuschl, Gunther" uniqKey="Deuschl G" first="Günther" last="Deuschl">Günther Deuschl</name><affiliation wicri:level="1"><nlm:aff id="af20"><addr-line>Department of Neurology</addr-line>,<institution>UKS-H, Campus Kiel; Christian-Albrechts-University</institution>,<addr-line>Kiel</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Durif, Franck" sort="Durif, Franck" uniqKey="Durif F" first="Franck" last="Durif">Franck Durif</name><affiliation wicri:level="1"><nlm:aff id="af21"><addr-line>Hôpital Gabriel Montpied, CHU de Grenoble, Department of Neurology</addr-line>,<addr-line>Clermont-Ferrand</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Pollak, Pierre" sort="Pollak, Pierre" uniqKey="Pollak P" first="Pierre" last="Pollak">Pierre Pollak</name><affiliation wicri:level="1"><nlm:aff id="af22"><addr-line>CHU de Grenoble, Department of Neurology</addr-line>,<addr-line>Grenoble</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Damier, Philippe" sort="Damier, Philippe" uniqKey="Damier P" first="Philippe" last="Damier">Philippe Damier</name><affiliation wicri:level="1"><nlm:aff id="af23"><addr-line>CHU de Nantes, Centre d'Investigation Clinique</addr-line>,<addr-line>Nantes</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Tison, Francois" sort="Tison, Francois" uniqKey="Tison F" first="François" last="Tison">François Tison</name><affiliation wicri:level="1"><nlm:aff id="af24"><addr-line>Hôpital Haut-Lévêque, Department of Neurology</addr-line>,<addr-line>Pessac</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Durr, Alexandra" sort="Durr, Alexandra" uniqKey="Durr A" first="Alexandra" last="Durr">Alexandra Durr</name><affiliation wicri:level="1"><nlm:aff id="af1"><institution>INSERM, UMR_S975</institution>,<addr-line>CR-ICM, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af2"><institution>UPMC University Paris 06, UMR_S975</institution>,<addr-line>CR-ICM, Pitié-Salpêtrière Hospital, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af3"><institution>CNRS UMR 7225</institution>,<addr-line>CR-ICM, Pitié-Salpêtrière Hospital, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af4"><addr-line>Assitance Publique Hôpitaux de Paris, Département de Génétique et Cytogénétique</addr-line>,<institution>Hôpital de la Pitié-Salpêtrière</institution>,<addr-line>Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Amouyel, Philippe" sort="Amouyel, Philippe" uniqKey="Amouyel P" first="Philippe" last="Amouyel">Philippe Amouyel</name><affiliation wicri:level="1"><nlm:aff id="af25"><institution>INSERM, U744</institution>,<addr-line>Lille</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af26"><institution>Institut Pasteur de Lille</institution>,<addr-line>Lille</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af27"><institution>Université Lille-Nord de France</institution>,<addr-line>Lille</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lambert, Jean Charles" sort="Lambert, Jean Charles" uniqKey="Lambert J" first="Jean-Charles" last="Lambert">Jean-Charles Lambert</name><affiliation wicri:level="1"><nlm:aff id="af25"><institution>INSERM, U744</institution>,<addr-line>Lille</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af26"><institution>Institut Pasteur de Lille</institution>,<addr-line>Lille</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af27"><institution>Université Lille-Nord de France</institution>,<addr-line>Lille</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Tzourio, Christophe" sort="Tzourio, Christophe" uniqKey="Tzourio C" first="Christophe" last="Tzourio">Christophe Tzourio</name><affiliation wicri:level="1"><nlm:aff id="af28"><institution>Université Pierre et Marie Curie—Paris 6, CNRS 7225 CRICM, ER4-UPMC Modélisation en recherche clinique, Hôpital Pitié-Salpêtrière</institution>,<addr-line>Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation><nlm:aff id="af29"><addr-line>INSERM UMR_S708, Neuroépidémiologie</addr-line>,<institution>Paris, France</institution></nlm:aff></affiliation></author><author><name sortKey="Maubaret, Cecilia" sort="Maubaret, Cecilia" uniqKey="Maubaret C" first="Cécilia" last="Maubaret">Cécilia Maubaret</name><affiliation wicri:level="1"><nlm:aff id="af30"><institution>INSERM U897, Université Bordeaux Ségalen</institution>,<addr-line>Bordeaux</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Charbonnier Beaupel, Fanny" sort="Charbonnier Beaupel, Fanny" uniqKey="Charbonnier Beaupel F" first="Fanny" last="Charbonnier-Beaupel">Fanny Charbonnier-Beaupel</name><affiliation wicri:level="1"><nlm:aff id="af1"><institution>INSERM, UMR_S975</institution>,<addr-line>CR-ICM, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af2"><institution>UPMC University Paris 06, UMR_S975</institution>,<addr-line>CR-ICM, Pitié-Salpêtrière Hospital, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af3"><institution>CNRS UMR 7225</institution>,<addr-line>CR-ICM, Pitié-Salpêtrière Hospital, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Tahiri, Khadija" sort="Tahiri, Khadija" uniqKey="Tahiri K" first="Khadija" last="Tahiri">Khadija Tahiri</name><affiliation wicri:level="1"><nlm:aff id="af1"><institution>INSERM, UMR_S975</institution>,<addr-line>CR-ICM, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af2"><institution>UPMC University Paris 06, UMR_S975</institution>,<addr-line>CR-ICM, Pitié-Salpêtrière Hospital, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af3"><institution>CNRS UMR 7225</institution>,<addr-line>CR-ICM, Pitié-Salpêtrière Hospital, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Vidailhet, Marie" sort="Vidailhet, Marie" uniqKey="Vidailhet M" first="Marie" last="Vidailhet">Marie Vidailhet</name><affiliation wicri:level="1"><nlm:aff id="af2"><institution>UPMC University Paris 06, UMR_S975</institution>,<addr-line>CR-ICM, Pitié-Salpêtrière Hospital, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af3"><institution>CNRS UMR 7225</institution>,<addr-line>CR-ICM, Pitié-Salpêtrière Hospital, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af6"><addr-line>Assistance Publique Hôpitaux de Paris, Department of Neurology</addr-line>,<institution>Hôpital de la Pitié-Salpêtrière</institution>,<addr-line>Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af31"><addr-line>“Movement Disorders and Basal Ganglia: Pathophysiology and experimental Therapeutics”</addr-line>,<institution>INSERM, UMR_S975</institution>,<addr-line>Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Martinez, Maria" sort="Martinez, Maria" uniqKey="Martinez M" first="Maria" last="Martinez">Maria Martinez</name><affiliation wicri:level="1"><nlm:aff id="af10"><institution>INSERM U1043, CPTP</institution>,<addr-line>Toulouse</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af11"><institution>Paul Sabatier University</institution>,<addr-line>Toulouse</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Brice, Alexis" sort="Brice, Alexis" uniqKey="Brice A" first="Alexis" last="Brice">Alexis Brice</name><affiliation wicri:level="1"><nlm:aff id="af1"><institution>INSERM, UMR_S975</institution>,<addr-line>CR-ICM, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af2"><institution>UPMC University Paris 06, UMR_S975</institution>,<addr-line>CR-ICM, Pitié-Salpêtrière Hospital, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af3"><institution>CNRS UMR 7225</institution>,<addr-line>CR-ICM, Pitié-Salpêtrière Hospital, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af4"><addr-line>Assitance Publique Hôpitaux de Paris, Département de Génétique et Cytogénétique</addr-line>,<institution>Hôpital de la Pitié-Salpêtrière</institution>,<addr-line>Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af6"><addr-line>Assistance Publique Hôpitaux de Paris, Department of Neurology</addr-line>,<institution>Hôpital de la Pitié-Salpêtrière</institution>,<addr-line>Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Corvol, Jean Christophe" sort="Corvol, Jean Christophe" uniqKey="Corvol J" first="Jean-Christophe" last="Corvol">Jean-Christophe Corvol</name><affiliation wicri:level="1"><nlm:aff id="af1"><institution>INSERM, UMR_S975</institution>,<addr-line>CR-ICM, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af2"><institution>UPMC University Paris 06, UMR_S975</institution>,<addr-line>CR-ICM, Pitié-Salpêtrière Hospital, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af3"><institution>CNRS UMR 7225</institution>,<addr-line>CR-ICM, Pitié-Salpêtrière Hospital, Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af5"><institution>INSERM, CIC-9503, Hôpital de la Pitié-Salpêtrière</institution>,<addr-line>Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af15"><addr-line>Assistance Publique Hôpitaux de Paris, Department of Pharmacology</addr-line>,<institution>Hôpital de la Pitié-Salpêtrière</institution>,<addr-line>Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Journal of Neurology, Neurosurgery, and Psychiatry</title><idno type="ISSN">0022-3050</idno><idno type="eISSN">1468-330X</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The catechol-O-methyltranferase (COMT) is one of the main enzymes that metabolise dopamine in the brain. The Val158Met polymorphism in the <italic>COMT</italic> gene (<italic>rs4680</italic>) causes a trimodal distribution of high (Val/Val), intermediate (Val/Met) and low (Met/Met) enzyme activity. We tested whether the Val158Met polymorphism is a modifier of the age at onset (AAO) in Parkinson's disease (PD). The <italic>rs4680</italic> was genotyped in a total of 16 609 subjects from five independent cohorts of European and North American origin (5886 patients with PD and 10 723 healthy controls). The multivariate analysis for comparing PD and control groups was based on a stepwise logistic regression, with gender, age and cohort origin included in the initial model. The multivariate analysis of the AAO was a mixed linear model, with <italic>COMT</italic> genotype and gender considered as fixed effects and cohort and cohort-gender interaction as random effects. <italic>COMT</italic> genotype was coded as a quantitative variable, assuming a codominant genetic effect. The distribution of the COMT polymorphism was not significantly different in patients and controls (p=0.22). The Val allele had a significant effect on the AAO with a younger AAO in patients with the Val/Val (57.1±13.9, p=0.03) than the Val/Met (57.4±13.9) and the Met/Met genotypes (58.3±13.5). The difference was greater in men (1.9 years between Val/Val and Met/Met, p=0.007) than in women (0.2 years, p=0.81). Thus, the Val158Met COMT polymorphism is not associated with PD in the Caucasian population but acts as a modifier of the AAO in PD with a sexual dimorphism: the Val allele is associated with a younger AAO in men with idiopathic PD.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Floderus, Y" uniqKey="Floderus Y">Y Floderus</name></author><author><name sortKey="Wetterberg, L" uniqKey="Wetterberg L">L Wetterberg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Weinshilboum, R" uniqKey="Weinshilboum R">R Weinshilboum</name></author><author><name sortKey="Raymond, F" uniqKey="Raymond F">F Raymond</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lotta, T" uniqKey="Lotta T">T Lotta</name></author><author><name sortKey="Vidgren, J" uniqKey="Vidgren J">J Vidgren</name></author><author><name sortKey="Tilgmann, C" uniqKey="Tilgmann C">C Tilgmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lachman, Hm" uniqKey="Lachman H">HM Lachman</name></author><author><name sortKey="Papolos, Df" uniqKey="Papolos D">DF Papolos</name></author><author><name sortKey="Saito, T" uniqKey="Saito T">T Saito</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcleod, Hl" uniqKey="Mcleod H">HL McLeod</name></author><author><name sortKey="Syvanen, Ac" uniqKey="Syvanen A">AC Syvanen</name></author><author><name sortKey="Githang A, J" uniqKey="Githang A J">J Githang'a</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hernan, Ma" uniqKey="Hernan M">MA Hernan</name></author><author><name sortKey="Checkoway, H" uniqKey="Checkoway H">H Checkoway</name></author><author><name sortKey="O Brien, R" uniqKey="O Brien R">R O'Brien</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Eerola, J" uniqKey="Eerola J">J 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uniqKey="Von Eberstein H">H von Eberstein</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nalls, Ma" uniqKey="Nalls M">MA Nalls</name></author><author><name sortKey="Plagnol, V" uniqKey="Plagnol V">V Plagnol</name></author><author><name sortKey="Hernandez, Dg" uniqKey="Hernandez D">DG Hernandez</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Simon Sanchez, J" uniqKey="Simon Sanchez J">J Simon-Sanchez</name></author><author><name sortKey="Schulte, C" uniqKey="Schulte C">C Schulte</name></author><author><name sortKey="Bras, Jm" uniqKey="Bras J">JM Bras</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Simon Sanchez, J" uniqKey="Simon Sanchez J">J Simon-Sanchez</name></author><author><name sortKey="Van Hilten, Jj" uniqKey="Van Hilten J">JJ van Hilten</name></author><author><name sortKey="Van De Warrenburg, B" uniqKey="Van De Warrenburg B">B van de Warrenburg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Spencer, Cc" uniqKey="Spencer C">CC Spencer</name></author><author><name sortKey="Plagnol, V" uniqKey="Plagnol V">V Plagnol</name></author><author><name sortKey="Strange, A" uniqKey="Strange A">A Strange</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Saad, M" uniqKey="Saad M">M Saad</name></author><author><name sortKey="Lesage, S" uniqKey="Lesage S">S Lesage</name></author><author><name sortKey="Saint Pierre, A" uniqKey="Saint Pierre A">A Saint-Pierre</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Li, Y" uniqKey="Li Y">Y Li</name></author><author><name sortKey="Willer, Cj" uniqKey="Willer C">CJ Willer</name></author><author><name sortKey="Ding, J" uniqKey="Ding J">J Ding</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Price, Al" uniqKey="Price A">AL 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<front><journal-meta><journal-id journal-id-type="nlm-ta">J Neurol Neurosurg Psychiatry</journal-id><journal-id journal-id-type="iso-abbrev">J. Neurol. Neurosurg. Psychiatr</journal-id><journal-id journal-id-type="hwp">jnnp</journal-id><journal-id journal-id-type="publisher-id">jnnp</journal-id><journal-title-group><journal-title>Journal of Neurology, Neurosurgery, and Psychiatry</journal-title></journal-title-group><issn pub-type="ppub">0022-3050</issn><issn pub-type="epub">1468-330X</issn><publisher><publisher-name>BMJ Publishing Group</publisher-name><publisher-loc>BMA House, Tavistock Square, London, WC1H 9JR</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">23408064</article-id><article-id pub-id-type="pmc">3646288</article-id><article-id pub-id-type="publisher-id">jnnp-2012-304475</article-id><article-id pub-id-type="doi">10.1136/jnnp-2012-304475</article-id><article-categories><subj-group subj-group-type="hwp-journal-coll"><subject>1506</subject></subj-group><subj-group subj-group-type="heading"><subject>Movement Disorders</subject></subj-group><series-title>Research paper</series-title></article-categories><title-group><article-title>The Val158Met COMT polymorphism is a modifier of the age at onset in Parkinson's disease with a sexual dimorphism</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Klebe</surname><given-names>Stephan</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="aff" rid="af2">2</xref><xref ref-type="aff" rid="af3">3</xref><xref ref-type="aff" rid="af4">4</xref><xref ref-type="aff" rid="af5">5</xref><xref ref-type="aff" rid="af6">6</xref><xref ref-type="aff" rid="af7">7</xref></contrib><contrib contrib-type="author"><name><surname>Golmard</surname><given-names>Jean-Louis</given-names></name><xref ref-type="aff" rid="af8">8</xref></contrib><contrib contrib-type="author"><name><surname>Nalls</surname><given-names>Michael A</given-names></name><xref ref-type="aff" rid="af9">9</xref></contrib><contrib 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rid="af13">13</xref></contrib><contrib contrib-type="author"><name><surname>Kuhlenbäumer</surname><given-names>Gregor</given-names></name><xref ref-type="aff" rid="af14">14</xref></contrib><contrib contrib-type="author"><name><surname>Charfi</surname><given-names>Rim</given-names></name><xref ref-type="aff" rid="af15">15</xref><xref ref-type="aff" rid="af16">16</xref></contrib><contrib contrib-type="author"><name><surname>Klein</surname><given-names>Christine</given-names></name><xref ref-type="aff" rid="af17">17</xref></contrib><contrib contrib-type="author"><name><surname>Hagenah</surname><given-names>Johann</given-names></name><xref ref-type="aff" rid="af17">17</xref></contrib><contrib contrib-type="author"><name><surname>Gasser</surname><given-names>Thomas</given-names></name><xref ref-type="aff" rid="af18">18</xref><xref ref-type="aff" rid="af19">19</xref></contrib><contrib contrib-type="author"><name><surname>Wurster</surname><given-names>Isabel</given-names></name><xref 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Silva</surname><given-names>Rohan</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Smith</surname><given-names>Colin</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Spencer</surname><given-names>Chris CA</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Stefánsson</surname><given-names>Hreinn</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Steinberg</surname><given-names>Stacy</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Stockton</surname><given-names>Joanna D</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Strange</surname><given-names>Amy</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Su</surname><given-names>Zhan</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Talbot</surname><given-names>Kevin</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Tanner</surname><given-names>Carlie M</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Tashakkori-Ghanbaria</surname><given-names>Avazeh</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Tison</surname><given-names>François</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Trabzuni</surname><given-names>Daniah</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Traynor</surname><given-names>Bryan J</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Uitterlinden</surname><given-names>G</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Vandrovcova</surname><given-names>Jana</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Velseboer</surname><given-names>Daan</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Vidailhet</surname><given-names>Marie</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Vukcevic</surname><given-names>Damjan</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Walker</surname><given-names>Robert</given-names></name></contrib><contrib contrib-type="collab"><name><surname>van de Warrenburg</surname><given-names>Bart</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Weale</surname><given-names>Michael E</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Wickremaratchi</surname><given-names>Mirdhu</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Williams</surname><given-names>Nigel</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Williams-Gray</surname><given-names>Caroline H</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Winder-Rhodes</surname><given-names>Sophie</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Martinez</surname><given-names>Maria</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Donnelly</surname><given-names>Peter</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Hardy</surname><given-names>John</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Heutink</surname><given-names>Peter</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Brice</surname><given-names>Alexis</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Gasser</surname><given-names>Thomas</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Wood</surname><given-names>Nicholas W</given-names></name></contrib><contrib contrib-type="collab"><name><surname>Singleton</surname><given-names>Andrew B</given-names></name></contrib></contrib-group><aff id="af1"><label>1</label><institution>INSERM, UMR_S975</institution>,<addr-line>CR-ICM, Paris</addr-line>,<country>France</country></aff><aff id="af2"><label>2</label><institution>UPMC University Paris 06, UMR_S975</institution>,<addr-line>CR-ICM, Pitié-Salpêtrière Hospital, Paris</addr-line>,<country>France</country></aff><aff id="af3"><label>3</label><institution>CNRS UMR 7225</institution>,<addr-line>CR-ICM, Pitié-Salpêtrière Hospital, Paris</addr-line>,<country>France</country></aff><aff id="af4"><label>4</label><addr-line>Assitance Publique Hôpitaux de Paris, Département de Génétique et Cytogénétique</addr-line>,<institution>Hôpital de la Pitié-Salpêtrière</institution>,<addr-line>Paris</addr-line>,<country>France</country></aff><aff id="af5"><label>5</label><institution>INSERM, CIC-9503, Hôpital de la Pitié-Salpêtrière</institution>,<addr-line>Paris</addr-line>,<country>France</country></aff><aff id="af6"><label>6</label><addr-line>Assistance Publique Hôpitaux de Paris, Department of Neurology</addr-line>,<institution>Hôpital de la Pitié-Salpêtrière</institution>,<addr-line>Paris</addr-line>,<country>France</country></aff><aff id="af7"><label>7</label><addr-line>Department of Neurology</addr-line>,<institution>University Hospital Würzburg</institution>,<addr-line>Würzburg</addr-line>,<country>Germany</country></aff><aff id="af8"><label>8</label><addr-line>Assistance Publique Hôpitaux de Paris, Department of Biostatistics</addr-line>,<institution>Hôpital de la Pitié-Salpêtrière</institution>,<addr-line>Paris</addr-line>,<country>France</country></aff><aff id="af9"><label>9</label><addr-line>Laboratory of Neurogenetics</addr-line>,<institution>National Institute on Aging, National Institutes of Health</institution>,<addr-line>Bethesda Maryland</addr-line>,<country>USA</country></aff><aff id="af10"><label>10</label><institution>INSERM U1043, CPTP</institution>,<addr-line>Toulouse</addr-line>,<country>France</country></aff><aff id="af11"><label>11</label><institution>Paul Sabatier University</institution>,<addr-line>Toulouse</addr-line>,<country>France</country></aff><aff id="af12"><label>12</label><addr-line>Department of Molecular Neuroscience</addr-line>,<institution>UCL Institute of Neurology</institution>,<addr-line>London</addr-line>,<country>UK</country></aff><aff id="af13"><label>13</label><addr-line>Department of Clinical Genetics Section of Medical Genomics</addr-line>,<institution>VU Medical Center</institution>,<addr-line>Amsterdam</addr-line>,<country>Netherlands</country></aff><aff id="af14"><label>14</label><institution>Institute of Experimental Medicine, Christian-Albrechts University</institution>,<addr-line>Kiel</addr-line>,<country>Germany</country></aff><aff id="af15"><label>15</label><addr-line>Assistance Publique Hôpitaux de Paris, Department of Pharmacology</addr-line>,<institution>Hôpital de la Pitié-Salpêtrière</institution>,<addr-line>Paris</addr-line>,<country>France</country></aff><aff id="af16"><label>16</label><addr-line>Faculté de Médecine de Tunis</addr-line>,<institution>Université de Tunis El Manar</institution>,<institution>Centre National de Pharmacovigilance de Tunis, Service de Pharmacologie Clinique</institution>,<addr-line>Tunis</addr-line>,<country>Tunisia</country></aff><aff id="af17"><label>17</label><addr-line>Institute of Neurogenetics</addr-line>,<institution>University of Lübeck</institution>,<addr-line>Lübeck</addr-line>,<country>Germany</country></aff><aff id="af18"><label>18</label><addr-line>Department of Neurodegenerative Diseases</addr-line>,<institution>Hertie-Institute for Clinical Brain Research, University of Tübingen</institution>,<addr-line>Tübingen</addr-line>,<country>Germany</country></aff><aff id="af19"><label>19</label><addr-line>Department of Neurodegenerative Diseases</addr-line>,<institution>German Center for Neurodegenerative Diseases (DZNE)</institution>,<addr-line>Tübingen</addr-line>,<country>Germany</country></aff><aff id="af20"><label>20</label><addr-line>Department of Neurology</addr-line>,<institution>UKS-H, Campus Kiel; Christian-Albrechts-University</institution>,<addr-line>Kiel</addr-line>,<country>Germany</country></aff><aff id="af21"><label>21</label><addr-line>Hôpital Gabriel Montpied, CHU de Grenoble, Department of Neurology</addr-line>,<addr-line>Clermont-Ferrand</addr-line>,<country>France</country></aff><aff id="af22"><label>22</label><addr-line>CHU de Grenoble, Department of Neurology</addr-line>,<addr-line>Grenoble</addr-line>,<country>France</country></aff><aff id="af23"><label>23</label><addr-line>CHU de Nantes, Centre d'Investigation Clinique</addr-line>,<addr-line>Nantes</addr-line>,<country>France</country></aff><aff id="af24"><label>24</label><addr-line>Hôpital Haut-Lévêque, Department of Neurology</addr-line>,<addr-line>Pessac</addr-line>,<country>France</country></aff><aff id="af25"><label>25</label><institution>INSERM, U744</institution>,<addr-line>Lille</addr-line>,<country>France</country></aff><aff id="af26"><label>26</label><institution>Institut Pasteur de Lille</institution>,<addr-line>Lille</addr-line>,<country>France</country></aff><aff id="af27"><label>27</label><institution>Université Lille-Nord de France</institution>,<addr-line>Lille</addr-line>,<country>France</country></aff><aff id="af28"><label>28</label><institution>Université Pierre et Marie Curie—Paris 6, CNRS 7225 CRICM, ER4-UPMC Modélisation en recherche clinique, Hôpital Pitié-Salpêtrière</institution>,<addr-line>Paris</addr-line>,<country>France</country></aff><aff id="af29"><label>29</label><addr-line>INSERM UMR_S708, Neuroépidémiologie</addr-line>,<institution>Paris, France</institution></aff><aff id="af30"><label>30</label><institution>INSERM U897, Université Bordeaux Ségalen</institution>,<addr-line>Bordeaux</addr-line>,<country>France</country></aff><aff id="af31"><label>31</label><addr-line>“Movement Disorders and Basal Ganglia: Pathophysiology and experimental Therapeutics”</addr-line>,<institution>INSERM, UMR_S975</institution>,<addr-line>Paris</addr-line>,<country>France</country></aff><author-notes><corresp><label>Correspondence to</label> Dr Jean-Christophe Corvol, Centre d'Investigation Clinique, Institut du Cerveau et de la Moelle épinière, Hôpital de la Pitié-Salpêtrière, 47 boulevard de l'Hôpital, Paris 75651 Cedex 13, France; <email>jean-christophe.corvol@psl.aphp.fr</email>.
</corresp></author-notes><pub-date pub-type="ppub"><month>6</month><year>2013</year></pub-date><pub-date pub-type="epub"><day>13</day><month>2</month><year>2013</year></pub-date><volume>84</volume><issue>6</issue><fpage>666</fpage><lpage>673</lpage><history><date date-type="received"><day>5</day><month>11</month><year>2012</year></date><date date-type="rev-recd"><day>4</day><month>1</month><year>2013</year></date><date date-type="accepted"><day>7</day><month>1</month><year>2013</year></date></history><permissions><copyright-statement>Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions</copyright-statement><copyright-year>2013</copyright-year><license license-type="open-access"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/">http://creativecommons.org/licenses/by-nc/3.0/</ext-link> and <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/legalcode">http://creativecommons.org/licenses/by-nc/3.0/legalcode</ext-link></license-p></license></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="jnnp-2012-304475.pdf"></self-uri><abstract><p>The catechol-O-methyltranferase (COMT) is one of the main enzymes that metabolise dopamine in the brain. The Val158Met polymorphism in the <italic>COMT</italic> gene (<italic>rs4680</italic>) causes a trimodal distribution of high (Val/Val), intermediate (Val/Met) and low (Met/Met) enzyme activity. We tested whether the Val158Met polymorphism is a modifier of the age at onset (AAO) in Parkinson's disease (PD). The <italic>rs4680</italic> was genotyped in a total of 16 609 subjects from five independent cohorts of European and North American origin (5886 patients with PD and 10 723 healthy controls). The multivariate analysis for comparing PD and control groups was based on a stepwise logistic regression, with gender, age and cohort origin included in the initial model. The multivariate analysis of the AAO was a mixed linear model, with <italic>COMT</italic> genotype and gender considered as fixed effects and cohort and cohort-gender interaction as random effects. <italic>COMT</italic> genotype was coded as a quantitative variable, assuming a codominant genetic effect. The distribution of the COMT polymorphism was not significantly different in patients and controls (p=0.22). The Val allele had a significant effect on the AAO with a younger AAO in patients with the Val/Val (57.1±13.9, p=0.03) than the Val/Met (57.4±13.9) and the Met/Met genotypes (58.3±13.5). The difference was greater in men (1.9 years between Val/Val and Met/Met, p=0.007) than in women (0.2 years, p=0.81). Thus, the Val158Met COMT polymorphism is not associated with PD in the Caucasian population but acts as a modifier of the AAO in PD with a sexual dimorphism: the Val allele is associated with a younger AAO in men with idiopathic PD.</p></abstract><kwd-group><kwd>Movement Disorders</kwd><kwd>Neurogenetics</kwd><kwd>Parkinson's Disease</kwd></kwd-group><custom-meta-group><custom-meta><meta-name>special-feature</meta-name><meta-value>unlocked</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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