Support of the histaminergic hypothesis in Tourette Syndrome: association of the histamine decarboxylase gene in a large sample of families
Identifieur interne : 000E97 ( Main/Exploration ); précédent : 000E96; suivant : 000E98Support of the histaminergic hypothesis in Tourette Syndrome: association of the histamine decarboxylase gene in a large sample of families
Auteurs : Iordanis Karagiannidis [Grèce] ; Sandra Dehning [Allemagne] ; Paul Sandor [Canada] ; Zsanett Tarnok [Hongrie] ; Renata Rizzo [Italie] ; Tomasz Wolanczyk [Pologne] ; Marcos Madruga-Garrido [Espagne] ; Johannes Hebebrand [Allemagne] ; Markus M. Nöthen [Allemagne] ; Gerd Lehmkuhl [Allemagne] ; Luca Farkas [Hongrie] ; Peter Nagy [Hongrie] ; Urszula Szymanska [Pologne] ; Zachos Anastasiou [Grèce] ; Vasileios Stathias [Grèce] ; Christos Androutsos [Grèce] ; Vaia Tsironi [Grèce] ; Anastasia Koumoula [Grèce] ; Csaba Barta [Hongrie] ; Peter Zill [Allemagne] ; Pablo Mir [Espagne] ; Norbert Müller [Allemagne] ; Cathy Barr [Canada] ; Peristera Paschou [Grèce]Source :
- Journal of Medical Genetics [ 0022-2593 ] ; 2013-11.
Abstract
Background Gilles de la Tourette Syndrome is a neurodevelopmental disorder that is caused by the interaction of environment with a complex genetic background. The genetic etiology of the disorder remains, so far, elusive, although multiple promising leads have been recently reported. The recent implication of the histamine decarboxylase (HDC) gene, the key enzyme in histamine production, raises the intriguing hypothesis of a possible role of histaminergic dysfunction leading to TS onset. Methods Following up on the finding of a nonsense mutation in a single family with TS, we investigated variation across the HDC gene for association with TS. As a result of a collaborative international effort, we studied a large sample of 520 nuclear families originating from seven European populations (Greek, Hungarian, Italian, Polish, German, Albanian, Spanish) as well as a sample collected in Canada. Results and Conclusions Interrogating 12 tagging SNPs (tSNP) across the HDC region, we find strong over-transmission of alleles at two SNPs (rs854150 and rs1894236) in the complete sample, as well as a statistically significant associated haplotypes. Analysis of individual populations also reveals signals of association in the Canadian, German and Italian samples. Our results provide strong support for the histaminergic hypothesis in TS etiology and point to a possible role of histamine pathways in neuronal development.
Url:
DOI: 10.1136/jmedgenet-2013-101637
Affiliations:
- Allemagne, Canada, Espagne, Grèce, Hongrie, Italie, Pologne
- Bavière, District de Cologne, District de Haute-Bavière, Hongrie centrale, Rhénanie-du-Nord-Westphalie
- Bonn, Budapest, Munich
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Nöthen</name><affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Genomics, Life and Brain Center, Institute for Human Genetics, University of Bonn, Bonn</wicri:regionArea><placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region><region type="district" nuts="2">District de Cologne</region><settlement type="city">Bonn</settlement></placeName></affiliation></author><author><name sortKey="Lehmkuhl, Gerd" sort="Lehmkuhl, Gerd" uniqKey="Lehmkuhl G" first="Gerd" last="Lehmkuhl">Gerd Lehmkuhl</name><affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Child and Adolescent, Psychiatry of the University of Cologne, Cologne</wicri:regionArea><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion></affiliation></author><author><name sortKey="Farkas, Luca" sort="Farkas, Luca" uniqKey="Farkas L" first="Luca" last="Farkas">Luca Farkas</name><affiliation wicri:level="3"><country xml:lang="fr">Hongrie</country><wicri:regionArea>Vadaskert Clinic for Child and Adolescent Psychiatry, Budapest</wicri:regionArea><placeName><settlement type="city">Budapest</settlement><region nuts="2">Hongrie centrale</region></placeName></affiliation></author><author><name sortKey="Nagy, Peter" sort="Nagy, Peter" uniqKey="Nagy P" first="Peter" last="Nagy">Peter Nagy</name><affiliation wicri:level="3"><country xml:lang="fr">Hongrie</country><wicri:regionArea>Vadaskert Clinic for Child and Adolescent Psychiatry, Budapest</wicri:regionArea><placeName><settlement type="city">Budapest</settlement><region nuts="2">Hongrie centrale</region></placeName></affiliation></author><author><name sortKey="Szymanska, Urszula" sort="Szymanska, Urszula" uniqKey="Szymanska U" first="Urszula" last="Szymanska">Urszula Szymanska</name><affiliation wicri:level="1"><country xml:lang="fr">Pologne</country><wicri:regionArea>Department of Child Psychiatry, Medical University of Warsaw, Warsaw</wicri:regionArea><wicri:noRegion>Warsaw</wicri:noRegion></affiliation></author><author><name sortKey="Anastasiou, Zachos" sort="Anastasiou, Zachos" uniqKey="Anastasiou Z" first="Zachos" last="Anastasiou">Zachos Anastasiou</name><affiliation wicri:level="1"><country xml:lang="fr">Grèce</country><wicri:regionArea>Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupoli</wicri:regionArea><wicri:noRegion>Alexandroupoli</wicri:noRegion></affiliation></author><author><name sortKey="Stathias, Vasileios" sort="Stathias, Vasileios" uniqKey="Stathias V" first="Vasileios" last="Stathias">Vasileios Stathias</name><affiliation wicri:level="1"><country xml:lang="fr">Grèce</country><wicri:regionArea>Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupoli</wicri:regionArea><wicri:noRegion>Alexandroupoli</wicri:noRegion></affiliation></author><author><name sortKey="Androutsos, Christos" sort="Androutsos, Christos" uniqKey="Androutsos C" first="Christos" last="Androutsos">Christos Androutsos</name><affiliation wicri:level="1"><country xml:lang="fr">Grèce</country><wicri:regionArea>Child and Adolescent Psychiatry Clinic, Sismanoglio General Hospital of Attica, Athens</wicri:regionArea><wicri:noRegion>Athens</wicri:noRegion></affiliation></author><author><name sortKey="Tsironi, Vaia" sort="Tsironi, Vaia" uniqKey="Tsironi V" first="Vaia" last="Tsironi">Vaia Tsironi</name><affiliation wicri:level="1"><country xml:lang="fr">Grèce</country><wicri:regionArea>Child and Adolescent Psychiatry Clinic, Sismanoglio General Hospital of Attica, Athens</wicri:regionArea><wicri:noRegion>Athens</wicri:noRegion></affiliation></author><author><name sortKey="Koumoula, Anastasia" sort="Koumoula, Anastasia" uniqKey="Koumoula A" first="Anastasia" last="Koumoula">Anastasia Koumoula</name><affiliation wicri:level="1"><country xml:lang="fr">Grèce</country><wicri:regionArea>Child and Adolescent Psychiatry Clinic, Sismanoglio General Hospital of Attica, Athens</wicri:regionArea><wicri:noRegion>Athens</wicri:noRegion></affiliation></author><author><name sortKey="Barta, Csaba" sort="Barta, Csaba" uniqKey="Barta C" first="Csaba" last="Barta">Csaba Barta</name><affiliation wicri:level="3"><country xml:lang="fr">Hongrie</country><wicri:regionArea>Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest</wicri:regionArea><placeName><settlement type="city">Budapest</settlement><region nuts="2">Hongrie centrale</region></placeName></affiliation></author><author><name sortKey="Zill, Peter" sort="Zill, Peter" uniqKey="Zill P" first="Peter" last="Zill">Peter Zill</name><affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Psychiatry, Ludwig-Maximilians-University Munich, Munich</wicri:regionArea><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName></affiliation></author><author><name sortKey="Mir, Pablo" sort="Mir, Pablo" uniqKey="Mir P" first="Pablo" last="Mir">Pablo Mir</name><affiliation wicri:level="1"><country xml:lang="fr">Espagne</country><wicri:regionArea>Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica/Sección de Neuropediatría, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville</wicri:regionArea><wicri:noRegion>Seville</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">Espagne</country><wicri:regionArea>Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Seville</wicri:regionArea><wicri:noRegion>Seville</wicri:noRegion></affiliation></author><author><name sortKey="Muller, Norbert" sort="Muller, Norbert" uniqKey="Muller N" first="Norbert" last="Müller">Norbert Müller</name><affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Psychiatry, Ludwig-Maximilians-University Munich, Munich</wicri:regionArea><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName></affiliation></author><author><name sortKey="Barr, Cathy" sort="Barr, Cathy" uniqKey="Barr C" first="Cathy" last="Barr">Cathy Barr</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Toronto Western Research Institute, University Health Network, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Paschou, Peristera" sort="Paschou, Peristera" uniqKey="Paschou P" first="Peristera" last="Paschou">Peristera Paschou</name><affiliation wicri:level="1"><country xml:lang="fr">Grèce</country><wicri:regionArea>Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupoli</wicri:regionArea><wicri:noRegion>Alexandroupoli</wicri:noRegion></affiliation></author></analytic><monogr></monogr><series><title level="j">Journal of Medical Genetics</title><title level="j" type="abbrev">J Med Genet</title><idno type="ISSN">0022-2593</idno><idno type="eISSN">1468-6244</idno><imprint><publisher>BMJ Publishing Group Ltd</publisher><date type="published" when="2013-11">2013-11</date><biblScope unit="volume">50</biblScope><biblScope unit="issue">11</biblScope><biblScope unit="page" from="760">760</biblScope></imprint><idno type="ISSN">0022-2593</idno></series><idno type="istex">F549E6BA0F178343BAE3B72D00B29778182D168C</idno><idno type="DOI">10.1136/jmedgenet-2013-101637</idno><idno type="href">jmedgenet-50-760.pdf</idno><idno type="ArticleID">jmedgenet-2013-101637</idno><idno type="PMID">23825391</idno><idno type="local">jmedgenet;50/11/760</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-2593</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Background Gilles de la Tourette Syndrome is a neurodevelopmental disorder that is caused by the interaction of environment with a complex genetic background. The genetic etiology of the disorder remains, so far, elusive, although multiple promising leads have been recently reported. The recent implication of the histamine decarboxylase (HDC) gene, the key enzyme in histamine production, raises the intriguing hypothesis of a possible role of histaminergic dysfunction leading to TS onset. Methods Following up on the finding of a nonsense mutation in a single family with TS, we investigated variation across the HDC gene for association with TS. As a result of a collaborative international effort, we studied a large sample of 520 nuclear families originating from seven European populations (Greek, Hungarian, Italian, Polish, German, Albanian, Spanish) as well as a sample collected in Canada. Results and Conclusions Interrogating 12 tagging SNPs (tSNP) across the HDC region, we find strong over-transmission of alleles at two SNPs (rs854150 and rs1894236) in the complete sample, as well as a statistically significant associated haplotypes. Analysis of individual populations also reveals signals of association in the Canadian, German and Italian samples. Our results provide strong support for the histaminergic hypothesis in TS etiology and point to a possible role of histamine pathways in neuronal development.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Canada</li><li>Espagne</li><li>Grèce</li><li>Hongrie</li><li>Italie</li><li>Pologne</li></country><region><li>Bavière</li><li>District de Cologne</li><li>District de Haute-Bavière</li><li>Hongrie centrale</li><li>Rhénanie-du-Nord-Westphalie</li></region><settlement><li>Bonn</li><li>Budapest</li><li>Munich</li></settlement></list><tree><country name="Grèce"><noRegion><name sortKey="Karagiannidis, Iordanis" sort="Karagiannidis, Iordanis" uniqKey="Karagiannidis I" first="Iordanis" last="Karagiannidis">Iordanis Karagiannidis</name></noRegion><name sortKey="Anastasiou, Zachos" sort="Anastasiou, Zachos" uniqKey="Anastasiou Z" first="Zachos" last="Anastasiou">Zachos Anastasiou</name><name sortKey="Androutsos, Christos" sort="Androutsos, Christos" uniqKey="Androutsos C" first="Christos" last="Androutsos">Christos Androutsos</name><name sortKey="Koumoula, Anastasia" sort="Koumoula, Anastasia" uniqKey="Koumoula A" first="Anastasia" last="Koumoula">Anastasia Koumoula</name><name sortKey="Paschou, Peristera" sort="Paschou, Peristera" uniqKey="Paschou P" first="Peristera" last="Paschou">Peristera Paschou</name><name sortKey="Stathias, Vasileios" sort="Stathias, Vasileios" uniqKey="Stathias V" first="Vasileios" last="Stathias">Vasileios Stathias</name><name sortKey="Tsironi, Vaia" sort="Tsironi, Vaia" uniqKey="Tsironi V" first="Vaia" last="Tsironi">Vaia Tsironi</name></country><country name="Allemagne"><region name="Bavière"><name sortKey="Dehning, Sandra" sort="Dehning, Sandra" uniqKey="Dehning S" first="Sandra" last="Dehning">Sandra Dehning</name></region><name sortKey="Hebebrand, Johannes" sort="Hebebrand, Johannes" uniqKey="Hebebrand J" first="Johannes" last="Hebebrand">Johannes Hebebrand</name><name sortKey="Lehmkuhl, Gerd" sort="Lehmkuhl, Gerd" uniqKey="Lehmkuhl G" first="Gerd" last="Lehmkuhl">Gerd Lehmkuhl</name><name sortKey="Muller, Norbert" sort="Muller, Norbert" uniqKey="Muller N" first="Norbert" last="Müller">Norbert Müller</name><name sortKey="Nothen, Markus M" sort="Nothen, Markus M" uniqKey="Nothen M" first="Markus M" last="Nöthen">Markus M. Nöthen</name><name sortKey="Zill, Peter" sort="Zill, Peter" uniqKey="Zill P" first="Peter" last="Zill">Peter Zill</name></country><country name="Canada"><noRegion><name sortKey="Sandor, Paul" sort="Sandor, Paul" uniqKey="Sandor P" first="Paul" last="Sandor">Paul Sandor</name></noRegion><name sortKey="Barr, Cathy" sort="Barr, Cathy" uniqKey="Barr C" first="Cathy" last="Barr">Cathy Barr</name></country><country name="Hongrie"><region name="Hongrie centrale"><name sortKey="Tarnok, Zsanett" sort="Tarnok, Zsanett" uniqKey="Tarnok Z" first="Zsanett" last="Tarnok">Zsanett Tarnok</name></region><name sortKey="Barta, Csaba" sort="Barta, Csaba" uniqKey="Barta C" first="Csaba" last="Barta">Csaba Barta</name><name sortKey="Farkas, Luca" sort="Farkas, Luca" uniqKey="Farkas L" first="Luca" last="Farkas">Luca Farkas</name><name sortKey="Nagy, Peter" sort="Nagy, Peter" uniqKey="Nagy P" first="Peter" last="Nagy">Peter Nagy</name></country><country name="Italie"><noRegion><name sortKey="Rizzo, Renata" sort="Rizzo, Renata" uniqKey="Rizzo R" first="Renata" last="Rizzo">Renata Rizzo</name></noRegion></country><country name="Pologne"><noRegion><name sortKey="Wolanczyk, Tomasz" sort="Wolanczyk, Tomasz" uniqKey="Wolanczyk T" first="Tomasz" last="Wolanczyk">Tomasz Wolanczyk</name></noRegion><name sortKey="Szymanska, Urszula" sort="Szymanska, Urszula" uniqKey="Szymanska U" first="Urszula" last="Szymanska">Urszula Szymanska</name></country><country name="Espagne"><noRegion><name sortKey="Madruga Garrido, Marcos" sort="Madruga Garrido, Marcos" uniqKey="Madruga Garrido M" first="Marcos" last="Madruga-Garrido">Marcos Madruga-Garrido</name></noRegion><name sortKey="Mir, Pablo" sort="Mir, Pablo" uniqKey="Mir P" first="Pablo" last="Mir">Pablo Mir</name><name sortKey="Mir, Pablo" sort="Mir, Pablo" uniqKey="Mir P" first="Pablo" last="Mir">Pablo Mir</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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