Polymorphism of the dopamine transporter type 1 gene modifies the treatment response in Parkinson's disease.
Identifieur interne : 000356 ( PubMed/Corpus ); précédent : 000355; suivant : 000357Polymorphism of the dopamine transporter type 1 gene modifies the treatment response in Parkinson's disease.
Auteurs : Caroline Moreau ; Sayah Meguig ; Jean-Christophe Corvol ; Julien Labreuche ; Francis Vasseur ; Alain Duhamel ; Arnaud Delval ; Thomas Bardyn ; Jean-Christophe Devedjian ; Nathalie Rouaix ; Gregory Petyt ; Christine Brefel-Courbon ; Fabienne Ory-Magne ; Dominique Guehl ; Alexandre Eusebio ; Valérie Fraix ; Pierre-Jean Saulnier ; Ouhaid Lagha-Boukbiza ; Frank Durif ; Mirela Faighel ; Caroline Giordana ; Sophie Drapier ; David Maltête ; Christine Tranchant ; Jean-Luc Houeto ; Bettina Debû ; Jean-Philippe Azulay ; François Tison ; Alain Destée ; Marie Vidailhet ; Olivier Rascol ; Kathy Dujardin ; Luc Defebvre ; Régis Bordet ; Bernard Sablonnière ; David DevosSource :
- Brain : a journal of neurology [ 1460-2156 ] ; 2015.
English descriptors
- KwdEn :
- Aged, Catechol O-Methyltransferase, Dopamine (metabolism), Dopamine Plasma Membrane Transport Proteins (genetics), Double-Blind Method, Genetic Predisposition to Disease (genetics), Genotype, Humans, Levodopa (therapeutic use), Middle Aged, Parkinson Disease (drug therapy), Parkinson Disease (genetics), Polymorphism, Genetic (genetics).
- MESH :
- chemical , genetics : Dopamine Plasma Membrane Transport Proteins.
- chemical , metabolism : Dopamine.
- chemical , therapeutic use : Levodopa.
- chemical : Catechol O-Methyltransferase.
- drug therapy : Parkinson Disease.
- genetics : Genetic Predisposition to Disease, Parkinson Disease, Polymorphism, Genetic.
- Aged, Double-Blind Method, Genotype, Humans, Middle Aged.
Abstract
After more than 50 years of treating Parkinson's disease with l-DOPA, there are still no guidelines on setting the optimal dose for a given patient. The dopamine transporter type 1, now known as solute carrier family 6 (neurotransmitter transporter), member 3 (SLC6A3) is the most powerful determinant of dopamine neurotransmission and might therefore influence the treatment response. We recently demonstrated that methylphenidate (a dopamine transporter inhibitor) is effective in patients with Parkinson's disease with motor and gait disorders. The objective of the present study was to determine whether genetic variants of the dopamine transporter type 1-encoding gene (SLC6A3) are associated with differences in the response to treatment of motor symptoms and gait disorders with l-DOPA and methylphenidate (with respect to the demographic, the disease and the treatment parameters and the other genes involved in the dopaminergic neurotransmission). This analysis was part of a multicentre, parallel-group, double-blind, placebo-controlled, randomized clinical trial of methylphenidate in Parkinson's disease (Protocol ID:2008-005801-20; ClinicalTrials.gov:NCT00914095). We scored the motor Unified Parkinson's Disease Rating Scale and the Stand-Walk-Sit Test before and after a standardized acute l-DOPA challenge before randomization and then after 3 months of methylphenidate treatment. Patients were screened for variants of genes involved in dopamine metabolism: rs28363170 and rs3836790 polymorphisms in the SLC6A3 gene, rs921451 and rs3837091 in the DDC gene (encoding the aromatic L-amino acid decarboxylase involved in the synthesis of dopamine from l-DOPA), rs1799836 in the MAOB gene (coding for monoamine oxidase B) and rs4680 in the COMT gene (coding for catechol-O-methyltransferase). Investigators and patients were blinded to the genotyping data throughout the study. Eighty-one subjects were genotyped and 61 were analysed for their acute motor response to l-DOPA. The SLC6A3 variants were significantly associated with greater efficacy of l-DOPA for motor symptoms. The SLC6A3 variants were also associated with greater efficacy of methylphenidate for motor symptoms and gait disorders in the ON l-DOPA condition. The difference between motor Unified Parkinson's Disease Rating Scale scores for patients with different SLC6A3 genotypes was statistically significant in a multivariate analysis that took account of other disease-related, treatment-related and pharmacogenetic parameters. Our preliminary results suggest that variants of SLC6A3 are genetic modifiers of the treatment response to l-DOPA and methylphenidate in Parkinson's disease. Further studies are required to assess the possible value of these genotypes for (i) guiding l-DOPA dose adaptations over the long term; and (ii) establishing the risk/benefit balance associated with methylphenidate treatment for gait disorders.
DOI: 10.1093/brain/awv063
PubMed: 25805645
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pubmed:25805645Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Polymorphism of the dopamine transporter type 1 gene modifies the treatment response in Parkinson's disease.</title><author><name sortKey="Moreau, Caroline" sort="Moreau, Caroline" uniqKey="Moreau C" first="Caroline" last="Moreau">Caroline Moreau</name><affiliation><nlm:affiliation>1 Department of Movement Disorders and Neurology, Lille University, CHU Lille, Lille, France 2 INSERM U1171, Lille University, Lille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Meguig, Sayah" sort="Meguig, Sayah" uniqKey="Meguig S" first="Sayah" last="Meguig">Sayah Meguig</name><affiliation><nlm:affiliation>3 Department of Molecular Biology and Pathology Centre, Lille University, CHU Lille, Lille, France.</nlm:affiliation></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><nlm:affiliation>4 Sorbonne Universités, UPMC Univ Paris 06, and INSERM UMRS_1127 and CIC_1422, and CNRS UMR_7225, and AP-HP, and ICM, Hôpital Pitié-Salpêtrière, Département des Maladies du Système Nerveux, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Labreuche, Julien" sort="Labreuche, Julien" uniqKey="Labreuche J" first="Julien" last="Labreuche">Julien Labreuche</name><affiliation><nlm:affiliation>5 Department of Biostatistics, Lille University, CHU Lille, Lille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Vasseur, Francis" sort="Vasseur, Francis" uniqKey="Vasseur F" first="Francis" last="Vasseur">Francis Vasseur</name><affiliation><nlm:affiliation>5 Department of Biostatistics, Lille University, CHU Lille, Lille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Duhamel, Alain" sort="Duhamel, Alain" uniqKey="Duhamel A" first="Alain" last="Duhamel">Alain Duhamel</name><affiliation><nlm:affiliation>5 Department of Biostatistics, Lille University, CHU Lille, Lille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Delval, Arnaud" sort="Delval, Arnaud" uniqKey="Delval A" first="Arnaud" last="Delval">Arnaud Delval</name><affiliation><nlm:affiliation>1 Department of Movement Disorders and Neurology, Lille University, CHU Lille, Lille, France 2 INSERM U1171, Lille University, Lille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Bardyn, Thomas" sort="Bardyn, Thomas" uniqKey="Bardyn T" first="Thomas" last="Bardyn">Thomas Bardyn</name><affiliation><nlm:affiliation>3 Department of Molecular Biology and Pathology Centre, Lille University, CHU Lille, Lille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Devedjian, Jean Christophe" sort="Devedjian, Jean Christophe" uniqKey="Devedjian J" first="Jean-Christophe" last="Devedjian">Jean-Christophe Devedjian</name><affiliation><nlm:affiliation>2 INSERM U1171, Lille University, Lille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Rouaix, Nathalie" sort="Rouaix, Nathalie" uniqKey="Rouaix N" first="Nathalie" last="Rouaix">Nathalie Rouaix</name><affiliation><nlm:affiliation>3 Department of Molecular Biology and Pathology Centre, Lille University, CHU Lille, Lille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Petyt, Gregory" sort="Petyt, Gregory" uniqKey="Petyt G" first="Gregory" last="Petyt">Gregory Petyt</name><affiliation><nlm:affiliation>6 Department of Nuclear Medicine, Lille University, CHU Lille, Lille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Brefel Courbon, Christine" sort="Brefel Courbon, Christine" uniqKey="Brefel Courbon C" first="Christine" last="Brefel-Courbon">Christine Brefel-Courbon</name><affiliation><nlm:affiliation>7 Departments of Clinical Pharmacology and Neurosciences, CIC9302, University Hospital and Paul Sabatier University, Toulouse, France.</nlm:affiliation></affiliation></author><author><name sortKey="Ory Magne, Fabienne" sort="Ory Magne, Fabienne" uniqKey="Ory Magne F" first="Fabienne" last="Ory-Magne">Fabienne Ory-Magne</name><affiliation><nlm:affiliation>7 Departments of Clinical Pharmacology and Neurosciences, CIC9302, University Hospital and Paul Sabatier University, Toulouse, France.</nlm:affiliation></affiliation></author><author><name sortKey="Guehl, Dominique" sort="Guehl, Dominique" uniqKey="Guehl D" first="Dominique" last="Guehl">Dominique Guehl</name><affiliation><nlm:affiliation>8 Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR CNRS 5293 and CHU de Bordeaux, Bordeaux, France.</nlm:affiliation></affiliation></author><author><name sortKey="Eusebio, Alexandre" sort="Eusebio, Alexandre" uniqKey="Eusebio A" first="Alexandre" last="Eusebio">Alexandre Eusebio</name><affiliation><nlm:affiliation>9 Department of Neurology and Movement Disorders - APHM Timone University Hospital and Institut de Neurosciences de la Timone, AMU-CNRS UMR 7289, Marseille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Fraix, Valerie" sort="Fraix, Valerie" uniqKey="Fraix V" first="Valérie" last="Fraix">Valérie Fraix</name><affiliation><nlm:affiliation>10 Department of Psychiatry and Neurology, CHU Grenoble, Grenoble, France.</nlm:affiliation></affiliation></author><author><name sortKey="Saulnier, Pierre Jean" sort="Saulnier, Pierre Jean" uniqKey="Saulnier P" first="Pierre-Jean" last="Saulnier">Pierre-Jean Saulnier</name><affiliation><nlm:affiliation>11 Department of Movement Disorders and Neurology, Centre d'Investigation Clinique, INSERM CIC 0802, INSERM U1084, Laboratoire de Neurosciences Expérimentales et Cliniques, CHU de Poitiers, Poitiers, France.</nlm:affiliation></affiliation></author><author><name sortKey="Lagha Boukbiza, Ouhaid" sort="Lagha Boukbiza, Ouhaid" uniqKey="Lagha Boukbiza O" first="Ouhaid" last="Lagha-Boukbiza">Ouhaid Lagha-Boukbiza</name><affiliation><nlm:affiliation>12 Department of Movement Disorders and Neurology, CHU Strasbourg, Strasbourg, France.</nlm:affiliation></affiliation></author><author><name sortKey="Durif, Frank" sort="Durif, Frank" uniqKey="Durif F" first="Frank" last="Durif">Frank Durif</name><affiliation><nlm:affiliation>13 Department of Movement Disorders and Neurology, CHU Clermont-Ferrand, Clermont-Ferrand, France.</nlm:affiliation></affiliation></author><author><name sortKey="Faighel, Mirela" sort="Faighel, Mirela" uniqKey="Faighel M" first="Mirela" last="Faighel">Mirela Faighel</name><affiliation><nlm:affiliation>14 Department of Movement Disorders and Neurology, INSERM, CIC04, CHU Nantes, Nantes, France.</nlm:affiliation></affiliation></author><author><name sortKey="Giordana, Caroline" sort="Giordana, Caroline" uniqKey="Giordana C" first="Caroline" last="Giordana">Caroline Giordana</name><affiliation><nlm:affiliation>15 Department of Movement Disorders and Neurology, CHU Nice, Nice, France.</nlm:affiliation></affiliation></author><author><name sortKey="Drapier, Sophie" sort="Drapier, Sophie" uniqKey="Drapier S" first="Sophie" last="Drapier">Sophie Drapier</name><affiliation><nlm:affiliation>16 Department of Neurology, EA- 425 Université Rennes 1 et CHU Pontchaillou, CHU Rennes, Rennes, France.</nlm:affiliation></affiliation></author><author><name sortKey="Maltete, David" sort="Maltete, David" uniqKey="Maltete D" first="David" last="Maltête">David Maltête</name><affiliation><nlm:affiliation>17 Department of Neurology and INSERM CIC-CRB 0204, Rouen University Hospital, CHU Rouen Rouen, France.</nlm:affiliation></affiliation></author><author><name sortKey="Tranchant, Christine" sort="Tranchant, Christine" uniqKey="Tranchant C" first="Christine" last="Tranchant">Christine Tranchant</name><affiliation><nlm:affiliation>12 Department of Movement Disorders and Neurology, CHU Strasbourg, Strasbourg, France.</nlm:affiliation></affiliation></author><author><name sortKey="Houeto, Jean Luc" sort="Houeto, Jean Luc" uniqKey="Houeto J" first="Jean-Luc" last="Houeto">Jean-Luc Houeto</name><affiliation><nlm:affiliation>11 Department of Movement Disorders and Neurology, Centre d'Investigation Clinique, INSERM CIC 0802, INSERM U1084, Laboratoire de Neurosciences Expérimentales et Cliniques, CHU de Poitiers, Poitiers, France.</nlm:affiliation></affiliation></author><author><name sortKey="Debu, Bettina" sort="Debu, Bettina" uniqKey="Debu B" first="Bettina" last="Debû">Bettina Debû</name><affiliation><nlm:affiliation>10 Department of Psychiatry and Neurology, CHU Grenoble, Grenoble, France.</nlm:affiliation></affiliation></author><author><name sortKey="Azulay, Jean Philippe" sort="Azulay, Jean Philippe" uniqKey="Azulay J" first="Jean-Philippe" last="Azulay">Jean-Philippe Azulay</name><affiliation><nlm:affiliation>9 Department of Neurology and Movement Disorders - APHM Timone University Hospital and Institut de Neurosciences de la Timone, AMU-CNRS UMR 7289, Marseille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Tison, Francois" sort="Tison, Francois" uniqKey="Tison F" first="François" last="Tison">François Tison</name><affiliation><nlm:affiliation>8 Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR CNRS 5293 and CHU de Bordeaux, Bordeaux, France.</nlm:affiliation></affiliation></author><author><name sortKey="Destee, Alain" sort="Destee, Alain" uniqKey="Destee A" first="Alain" last="Destée">Alain Destée</name><affiliation><nlm:affiliation>1 Department of Movement Disorders and Neurology, Lille University, CHU Lille, Lille, France 18 INSERM U837/6 Lille JPARC, France.</nlm:affiliation></affiliation></author><author><name sortKey="Vidailhet, Marie" sort="Vidailhet, Marie" uniqKey="Vidailhet M" first="Marie" last="Vidailhet">Marie Vidailhet</name><affiliation><nlm:affiliation>6 Department of Nuclear Medicine, Lille University, CHU Lille, Lille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Rascol, Olivier" sort="Rascol, Olivier" uniqKey="Rascol O" first="Olivier" last="Rascol">Olivier Rascol</name><affiliation><nlm:affiliation>7 Departments of Clinical Pharmacology and Neurosciences, CIC9302, University Hospital and Paul Sabatier University, Toulouse, France 19 INSERM NS-PARK National Network, France.</nlm:affiliation></affiliation></author><author><name sortKey="Dujardin, Kathy" sort="Dujardin, Kathy" uniqKey="Dujardin K" first="Kathy" last="Dujardin">Kathy Dujardin</name><affiliation><nlm:affiliation>1 Department of Movement Disorders and Neurology, Lille University, CHU Lille, Lille, France 2 INSERM U1171, Lille University, Lille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Defebvre, Luc" sort="Defebvre, Luc" uniqKey="Defebvre L" first="Luc" last="Defebvre">Luc Defebvre</name><affiliation><nlm:affiliation>1 Department of Movement Disorders and Neurology, Lille University, CHU Lille, Lille, France 2 INSERM U1171, Lille University, Lille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Bordet, Regis" sort="Bordet, Regis" uniqKey="Bordet R" first="Régis" last="Bordet">Régis Bordet</name><affiliation><nlm:affiliation>2 INSERM U1171, Lille University, Lille, France 18 INSERM U837/6 Lille JPARC, France.</nlm:affiliation></affiliation></author><author><name sortKey="Sablonniere, Bernard" sort="Sablonniere, Bernard" uniqKey="Sablonniere B" first="Bernard" last="Sablonnière">Bernard Sablonnière</name><affiliation><nlm:affiliation>3 Department of Molecular Biology and Pathology Centre, Lille University, CHU Lille, Lille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Devos, David" sort="Devos, David" uniqKey="Devos D" first="David" last="Devos">David Devos</name><affiliation><nlm:affiliation>1 Department of Movement Disorders and Neurology, Lille University, CHU Lille, Lille, France 2 INSERM U1171, Lille University, Lille, France 20 Department of Medical Pharmacology, Lille University, CHU Lille, Lille, France david.devos@chru-lille.fr.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2015">2015</date><idno type="RBID">pubmed:25805645</idno><idno type="pmid">25805645</idno><idno type="doi">10.1093/brain/awv063</idno><idno type="wicri:Area/PubMed/Corpus">000356</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000356</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Polymorphism of the dopamine transporter type 1 gene modifies the treatment response in Parkinson's disease.</title><author><name sortKey="Moreau, Caroline" sort="Moreau, Caroline" uniqKey="Moreau C" first="Caroline" last="Moreau">Caroline Moreau</name><affiliation><nlm:affiliation>1 Department of Movement Disorders and Neurology, Lille University, CHU Lille, Lille, France 2 INSERM U1171, Lille University, Lille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Meguig, Sayah" sort="Meguig, Sayah" uniqKey="Meguig S" first="Sayah" last="Meguig">Sayah Meguig</name><affiliation><nlm:affiliation>3 Department of Molecular Biology and Pathology Centre, Lille University, CHU Lille, Lille, France.</nlm:affiliation></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><nlm:affiliation>4 Sorbonne Universités, UPMC Univ Paris 06, and INSERM UMRS_1127 and CIC_1422, and CNRS UMR_7225, and AP-HP, and ICM, Hôpital Pitié-Salpêtrière, Département des Maladies du Système Nerveux, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Labreuche, Julien" sort="Labreuche, Julien" uniqKey="Labreuche J" first="Julien" last="Labreuche">Julien Labreuche</name><affiliation><nlm:affiliation>5 Department of Biostatistics, Lille University, CHU Lille, Lille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Vasseur, Francis" sort="Vasseur, Francis" uniqKey="Vasseur F" first="Francis" last="Vasseur">Francis Vasseur</name><affiliation><nlm:affiliation>5 Department of Biostatistics, Lille University, CHU Lille, Lille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Duhamel, Alain" sort="Duhamel, Alain" uniqKey="Duhamel A" first="Alain" last="Duhamel">Alain Duhamel</name><affiliation><nlm:affiliation>5 Department of Biostatistics, Lille University, CHU Lille, Lille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Delval, Arnaud" sort="Delval, Arnaud" uniqKey="Delval A" first="Arnaud" last="Delval">Arnaud Delval</name><affiliation><nlm:affiliation>1 Department of Movement Disorders and Neurology, Lille University, CHU Lille, Lille, France 2 INSERM U1171, Lille University, Lille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Bardyn, Thomas" sort="Bardyn, Thomas" uniqKey="Bardyn T" first="Thomas" last="Bardyn">Thomas Bardyn</name><affiliation><nlm:affiliation>3 Department of Molecular Biology and Pathology Centre, Lille University, CHU Lille, Lille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Devedjian, Jean Christophe" sort="Devedjian, Jean Christophe" uniqKey="Devedjian J" first="Jean-Christophe" last="Devedjian">Jean-Christophe Devedjian</name><affiliation><nlm:affiliation>2 INSERM U1171, Lille University, Lille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Rouaix, Nathalie" sort="Rouaix, Nathalie" uniqKey="Rouaix N" first="Nathalie" last="Rouaix">Nathalie Rouaix</name><affiliation><nlm:affiliation>3 Department of Molecular Biology and Pathology Centre, Lille University, CHU Lille, Lille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Petyt, Gregory" sort="Petyt, Gregory" uniqKey="Petyt G" first="Gregory" last="Petyt">Gregory Petyt</name><affiliation><nlm:affiliation>6 Department of Nuclear Medicine, Lille University, CHU Lille, Lille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Brefel Courbon, Christine" sort="Brefel Courbon, Christine" uniqKey="Brefel Courbon C" first="Christine" last="Brefel-Courbon">Christine Brefel-Courbon</name><affiliation><nlm:affiliation>7 Departments of Clinical Pharmacology and Neurosciences, CIC9302, University Hospital and Paul Sabatier University, Toulouse, France.</nlm:affiliation></affiliation></author><author><name sortKey="Ory Magne, Fabienne" sort="Ory Magne, Fabienne" uniqKey="Ory Magne F" first="Fabienne" last="Ory-Magne">Fabienne Ory-Magne</name><affiliation><nlm:affiliation>7 Departments of Clinical Pharmacology and Neurosciences, CIC9302, University Hospital and Paul Sabatier University, Toulouse, France.</nlm:affiliation></affiliation></author><author><name sortKey="Guehl, Dominique" sort="Guehl, Dominique" uniqKey="Guehl D" first="Dominique" last="Guehl">Dominique Guehl</name><affiliation><nlm:affiliation>8 Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR CNRS 5293 and CHU de Bordeaux, Bordeaux, France.</nlm:affiliation></affiliation></author><author><name sortKey="Eusebio, Alexandre" sort="Eusebio, Alexandre" uniqKey="Eusebio A" first="Alexandre" last="Eusebio">Alexandre Eusebio</name><affiliation><nlm:affiliation>9 Department of Neurology and Movement Disorders - APHM Timone University Hospital and Institut de Neurosciences de la Timone, AMU-CNRS UMR 7289, Marseille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Fraix, Valerie" sort="Fraix, Valerie" uniqKey="Fraix V" first="Valérie" last="Fraix">Valérie Fraix</name><affiliation><nlm:affiliation>10 Department of Psychiatry and Neurology, CHU Grenoble, Grenoble, France.</nlm:affiliation></affiliation></author><author><name sortKey="Saulnier, Pierre Jean" sort="Saulnier, Pierre Jean" uniqKey="Saulnier P" first="Pierre-Jean" last="Saulnier">Pierre-Jean Saulnier</name><affiliation><nlm:affiliation>11 Department of Movement Disorders and Neurology, Centre d'Investigation Clinique, INSERM CIC 0802, INSERM U1084, Laboratoire de Neurosciences Expérimentales et Cliniques, CHU de Poitiers, Poitiers, France.</nlm:affiliation></affiliation></author><author><name sortKey="Lagha Boukbiza, Ouhaid" sort="Lagha Boukbiza, Ouhaid" uniqKey="Lagha Boukbiza O" first="Ouhaid" last="Lagha-Boukbiza">Ouhaid Lagha-Boukbiza</name><affiliation><nlm:affiliation>12 Department of Movement Disorders and Neurology, CHU Strasbourg, Strasbourg, France.</nlm:affiliation></affiliation></author><author><name sortKey="Durif, Frank" sort="Durif, Frank" uniqKey="Durif F" first="Frank" last="Durif">Frank Durif</name><affiliation><nlm:affiliation>13 Department of Movement Disorders and Neurology, CHU Clermont-Ferrand, Clermont-Ferrand, France.</nlm:affiliation></affiliation></author><author><name sortKey="Faighel, Mirela" sort="Faighel, Mirela" uniqKey="Faighel M" first="Mirela" last="Faighel">Mirela Faighel</name><affiliation><nlm:affiliation>14 Department of Movement Disorders and Neurology, INSERM, CIC04, CHU Nantes, Nantes, France.</nlm:affiliation></affiliation></author><author><name sortKey="Giordana, Caroline" sort="Giordana, Caroline" uniqKey="Giordana C" first="Caroline" last="Giordana">Caroline Giordana</name><affiliation><nlm:affiliation>15 Department of Movement Disorders and Neurology, CHU Nice, Nice, France.</nlm:affiliation></affiliation></author><author><name sortKey="Drapier, Sophie" sort="Drapier, Sophie" uniqKey="Drapier S" first="Sophie" last="Drapier">Sophie Drapier</name><affiliation><nlm:affiliation>16 Department of Neurology, EA- 425 Université Rennes 1 et CHU Pontchaillou, CHU Rennes, Rennes, France.</nlm:affiliation></affiliation></author><author><name sortKey="Maltete, David" sort="Maltete, David" uniqKey="Maltete D" first="David" last="Maltête">David Maltête</name><affiliation><nlm:affiliation>17 Department of Neurology and INSERM CIC-CRB 0204, Rouen University Hospital, CHU Rouen Rouen, France.</nlm:affiliation></affiliation></author><author><name sortKey="Tranchant, Christine" sort="Tranchant, Christine" uniqKey="Tranchant C" first="Christine" last="Tranchant">Christine Tranchant</name><affiliation><nlm:affiliation>12 Department of Movement Disorders and Neurology, CHU Strasbourg, Strasbourg, France.</nlm:affiliation></affiliation></author><author><name sortKey="Houeto, Jean Luc" sort="Houeto, Jean Luc" uniqKey="Houeto J" first="Jean-Luc" last="Houeto">Jean-Luc Houeto</name><affiliation><nlm:affiliation>11 Department of Movement Disorders and Neurology, Centre d'Investigation Clinique, INSERM CIC 0802, INSERM U1084, Laboratoire de Neurosciences Expérimentales et Cliniques, CHU de Poitiers, Poitiers, France.</nlm:affiliation></affiliation></author><author><name sortKey="Debu, Bettina" sort="Debu, Bettina" uniqKey="Debu B" first="Bettina" last="Debû">Bettina Debû</name><affiliation><nlm:affiliation>10 Department of Psychiatry and Neurology, CHU Grenoble, Grenoble, France.</nlm:affiliation></affiliation></author><author><name sortKey="Azulay, Jean Philippe" sort="Azulay, Jean Philippe" uniqKey="Azulay J" first="Jean-Philippe" last="Azulay">Jean-Philippe Azulay</name><affiliation><nlm:affiliation>9 Department of Neurology and Movement Disorders - APHM Timone University Hospital and Institut de Neurosciences de la Timone, AMU-CNRS UMR 7289, Marseille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Tison, Francois" sort="Tison, Francois" uniqKey="Tison F" first="François" last="Tison">François Tison</name><affiliation><nlm:affiliation>8 Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR CNRS 5293 and CHU de Bordeaux, Bordeaux, France.</nlm:affiliation></affiliation></author><author><name sortKey="Destee, Alain" sort="Destee, Alain" uniqKey="Destee A" first="Alain" last="Destée">Alain Destée</name><affiliation><nlm:affiliation>1 Department of Movement Disorders and Neurology, Lille University, CHU Lille, Lille, France 18 INSERM U837/6 Lille JPARC, France.</nlm:affiliation></affiliation></author><author><name sortKey="Vidailhet, Marie" sort="Vidailhet, Marie" uniqKey="Vidailhet M" first="Marie" last="Vidailhet">Marie Vidailhet</name><affiliation><nlm:affiliation>6 Department of Nuclear Medicine, Lille University, CHU Lille, Lille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Rascol, Olivier" sort="Rascol, Olivier" uniqKey="Rascol O" first="Olivier" last="Rascol">Olivier Rascol</name><affiliation><nlm:affiliation>7 Departments of Clinical Pharmacology and Neurosciences, CIC9302, University Hospital and Paul Sabatier University, Toulouse, France 19 INSERM NS-PARK National Network, France.</nlm:affiliation></affiliation></author><author><name sortKey="Dujardin, Kathy" sort="Dujardin, Kathy" uniqKey="Dujardin K" first="Kathy" last="Dujardin">Kathy Dujardin</name><affiliation><nlm:affiliation>1 Department of Movement Disorders and Neurology, Lille University, CHU Lille, Lille, France 2 INSERM U1171, Lille University, Lille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Defebvre, Luc" sort="Defebvre, Luc" uniqKey="Defebvre L" first="Luc" last="Defebvre">Luc Defebvre</name><affiliation><nlm:affiliation>1 Department of Movement Disorders and Neurology, Lille University, CHU Lille, Lille, France 2 INSERM U1171, Lille University, Lille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Bordet, Regis" sort="Bordet, Regis" uniqKey="Bordet R" first="Régis" last="Bordet">Régis Bordet</name><affiliation><nlm:affiliation>2 INSERM U1171, Lille University, Lille, France 18 INSERM U837/6 Lille JPARC, France.</nlm:affiliation></affiliation></author><author><name sortKey="Sablonniere, Bernard" sort="Sablonniere, Bernard" uniqKey="Sablonniere B" first="Bernard" last="Sablonnière">Bernard Sablonnière</name><affiliation><nlm:affiliation>3 Department of Molecular Biology and Pathology Centre, Lille University, CHU Lille, Lille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Devos, David" sort="Devos, David" uniqKey="Devos D" first="David" last="Devos">David Devos</name><affiliation><nlm:affiliation>1 Department of Movement Disorders and Neurology, Lille University, CHU Lille, Lille, France 2 INSERM U1171, Lille University, Lille, France 20 Department of Medical Pharmacology, Lille University, CHU Lille, Lille, France david.devos@chru-lille.fr.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Brain : a journal of neurology</title><idno type="eISSN">1460-2156</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term><term>Catechol O-Methyltransferase</term><term>Dopamine (metabolism)</term><term>Dopamine Plasma Membrane Transport Proteins (genetics)</term><term>Double-Blind Method</term><term>Genetic Predisposition to Disease (genetics)</term><term>Genotype</term><term>Humans</term><term>Levodopa (therapeutic use)</term><term>Middle Aged</term><term>Parkinson Disease (drug therapy)</term><term>Parkinson Disease (genetics)</term><term>Polymorphism, Genetic (genetics)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Dopamine Plasma Membrane Transport Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Dopamine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Levodopa</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Catechol O-Methyltransferase</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Genetic Predisposition to Disease</term><term>Parkinson Disease</term><term>Polymorphism, Genetic</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Double-Blind Method</term><term>Genotype</term><term>Humans</term><term>Middle Aged</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">After more than 50 years of treating Parkinson's disease with l-DOPA, there are still no guidelines on setting the optimal dose for a given patient. The dopamine transporter type 1, now known as solute carrier family 6 (neurotransmitter transporter), member 3 (SLC6A3) is the most powerful determinant of dopamine neurotransmission and might therefore influence the treatment response. We recently demonstrated that methylphenidate (a dopamine transporter inhibitor) is effective in patients with Parkinson's disease with motor and gait disorders. The objective of the present study was to determine whether genetic variants of the dopamine transporter type 1-encoding gene (SLC6A3) are associated with differences in the response to treatment of motor symptoms and gait disorders with l-DOPA and methylphenidate (with respect to the demographic, the disease and the treatment parameters and the other genes involved in the dopaminergic neurotransmission). This analysis was part of a multicentre, parallel-group, double-blind, placebo-controlled, randomized clinical trial of methylphenidate in Parkinson's disease (Protocol ID:2008-005801-20; ClinicalTrials.gov:NCT00914095). We scored the motor Unified Parkinson's Disease Rating Scale and the Stand-Walk-Sit Test before and after a standardized acute l-DOPA challenge before randomization and then after 3 months of methylphenidate treatment. Patients were screened for variants of genes involved in dopamine metabolism: rs28363170 and rs3836790 polymorphisms in the SLC6A3 gene, rs921451 and rs3837091 in the DDC gene (encoding the aromatic L-amino acid decarboxylase involved in the synthesis of dopamine from l-DOPA), rs1799836 in the MAOB gene (coding for monoamine oxidase B) and rs4680 in the COMT gene (coding for catechol-O-methyltransferase). Investigators and patients were blinded to the genotyping data throughout the study. Eighty-one subjects were genotyped and 61 were analysed for their acute motor response to l-DOPA. The SLC6A3 variants were significantly associated with greater efficacy of l-DOPA for motor symptoms. The SLC6A3 variants were also associated with greater efficacy of methylphenidate for motor symptoms and gait disorders in the ON l-DOPA condition. The difference between motor Unified Parkinson's Disease Rating Scale scores for patients with different SLC6A3 genotypes was statistically significant in a multivariate analysis that took account of other disease-related, treatment-related and pharmacogenetic parameters. Our preliminary results suggest that variants of SLC6A3 are genetic modifiers of the treatment response to l-DOPA and methylphenidate in Parkinson's disease. Further studies are required to assess the possible value of these genotypes for (i) guiding l-DOPA dose adaptations over the long term; and (ii) establishing the risk/benefit balance associated with methylphenidate treatment for gait disorders.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">25805645</PMID><DateCreated><Year>2015</Year><Month>04</Month><Day>24</Day></DateCreated><DateCompleted><Year>2015</Year><Month>07</Month><Day>17</Day></DateCompleted><DateRevised><Year>2015</Year><Month>04</Month><Day>24</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1460-2156</ISSN><JournalIssue CitedMedium="Internet"><Volume>138</Volume><Issue>Pt 5</Issue><PubDate><Year>2015</Year><Month>May</Month></PubDate></JournalIssue><Title>Brain : a journal of neurology</Title><ISOAbbreviation>Brain</ISOAbbreviation></Journal><ArticleTitle>Polymorphism of the dopamine transporter type 1 gene modifies the treatment response in Parkinson's disease.</ArticleTitle><Pagination><MedlinePgn>1271-83</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1093/brain/awv063</ELocationID><Abstract><AbstractText>After more than 50 years of treating Parkinson's disease with l-DOPA, there are still no guidelines on setting the optimal dose for a given patient. The dopamine transporter type 1, now known as solute carrier family 6 (neurotransmitter transporter), member 3 (SLC6A3) is the most powerful determinant of dopamine neurotransmission and might therefore influence the treatment response. We recently demonstrated that methylphenidate (a dopamine transporter inhibitor) is effective in patients with Parkinson's disease with motor and gait disorders. The objective of the present study was to determine whether genetic variants of the dopamine transporter type 1-encoding gene (SLC6A3) are associated with differences in the response to treatment of motor symptoms and gait disorders with l-DOPA and methylphenidate (with respect to the demographic, the disease and the treatment parameters and the other genes involved in the dopaminergic neurotransmission). This analysis was part of a multicentre, parallel-group, double-blind, placebo-controlled, randomized clinical trial of methylphenidate in Parkinson's disease (Protocol ID:2008-005801-20; ClinicalTrials.gov:NCT00914095). We scored the motor Unified Parkinson's Disease Rating Scale and the Stand-Walk-Sit Test before and after a standardized acute l-DOPA challenge before randomization and then after 3 months of methylphenidate treatment. Patients were screened for variants of genes involved in dopamine metabolism: rs28363170 and rs3836790 polymorphisms in the SLC6A3 gene, rs921451 and rs3837091 in the DDC gene (encoding the aromatic L-amino acid decarboxylase involved in the synthesis of dopamine from l-DOPA), rs1799836 in the MAOB gene (coding for monoamine oxidase B) and rs4680 in the COMT gene (coding for catechol-O-methyltransferase). Investigators and patients were blinded to the genotyping data throughout the study. Eighty-one subjects were genotyped and 61 were analysed for their acute motor response to l-DOPA. The SLC6A3 variants were significantly associated with greater efficacy of l-DOPA for motor symptoms. The SLC6A3 variants were also associated with greater efficacy of methylphenidate for motor symptoms and gait disorders in the ON l-DOPA condition. The difference between motor Unified Parkinson's Disease Rating Scale scores for patients with different SLC6A3 genotypes was statistically significant in a multivariate analysis that took account of other disease-related, treatment-related and pharmacogenetic parameters. Our preliminary results suggest that variants of SLC6A3 are genetic modifiers of the treatment response to l-DOPA and methylphenidate in Parkinson's disease. Further studies are required to assess the possible value of these genotypes for (i) guiding l-DOPA dose adaptations over the long term; and (ii) establishing the risk/benefit balance associated with methylphenidate treatment for gait disorders.</AbstractText><CopyrightInformation>© The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Moreau</LastName><ForeName>Caroline</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>1 Department of Movement Disorders and Neurology, Lille University, CHU Lille, Lille, France 2 INSERM U1171, Lille University, Lille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Meguig</LastName><ForeName>Sayah</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>3 Department of Molecular Biology and Pathology Centre, Lille University, CHU Lille, Lille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Corvol</LastName><ForeName>Jean-Christophe</ForeName><Initials>JC</Initials><AffiliationInfo><Affiliation>4 Sorbonne Universités, UPMC Univ Paris 06, and INSERM UMRS_1127 and CIC_1422, and CNRS UMR_7225, and AP-HP, and ICM, Hôpital Pitié-Salpêtrière, Département des Maladies du Système Nerveux, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Labreuche</LastName><ForeName>Julien</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>5 Department of Biostatistics, Lille University, CHU Lille, Lille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vasseur</LastName><ForeName>Francis</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>5 Department of Biostatistics, Lille University, CHU Lille, Lille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Duhamel</LastName><ForeName>Alain</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>5 Department of Biostatistics, Lille University, CHU Lille, Lille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Delval</LastName><ForeName>Arnaud</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>1 Department of Movement Disorders and Neurology, Lille University, CHU Lille, Lille, France 2 INSERM U1171, Lille University, Lille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bardyn</LastName><ForeName>Thomas</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>3 Department of Molecular Biology and Pathology Centre, Lille University, CHU Lille, Lille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Devedjian</LastName><ForeName>Jean-Christophe</ForeName><Initials>JC</Initials><AffiliationInfo><Affiliation>2 INSERM U1171, Lille University, Lille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rouaix</LastName><ForeName>Nathalie</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>3 Department of Molecular Biology and Pathology Centre, Lille University, CHU Lille, Lille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Petyt</LastName><ForeName>Gregory</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>6 Department of Nuclear Medicine, Lille University, CHU Lille, Lille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Brefel-Courbon</LastName><ForeName>Christine</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>7 Departments of Clinical Pharmacology and Neurosciences, CIC9302, University Hospital and Paul Sabatier University, Toulouse, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ory-Magne</LastName><ForeName>Fabienne</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>7 Departments of Clinical Pharmacology and Neurosciences, CIC9302, University Hospital and Paul Sabatier University, Toulouse, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Guehl</LastName><ForeName>Dominique</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>8 Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR CNRS 5293 and CHU de Bordeaux, Bordeaux, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Eusebio</LastName><ForeName>Alexandre</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>9 Department of Neurology and Movement Disorders - APHM Timone University Hospital and Institut de Neurosciences de la Timone, AMU-CNRS UMR 7289, Marseille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fraix</LastName><ForeName>Valérie</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>10 Department of Psychiatry and Neurology, CHU Grenoble, Grenoble, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Saulnier</LastName><ForeName>Pierre-Jean</ForeName><Initials>PJ</Initials><AffiliationInfo><Affiliation>11 Department of Movement Disorders and Neurology, Centre d'Investigation Clinique, INSERM CIC 0802, INSERM U1084, Laboratoire de Neurosciences Expérimentales et Cliniques, CHU de Poitiers, Poitiers, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lagha-Boukbiza</LastName><ForeName>Ouhaid</ForeName><Initials>O</Initials><AffiliationInfo><Affiliation>12 Department of Movement Disorders and Neurology, CHU Strasbourg, Strasbourg, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Durif</LastName><ForeName>Frank</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>13 Department of Movement Disorders and Neurology, CHU Clermont-Ferrand, Clermont-Ferrand, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Faighel</LastName><ForeName>Mirela</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>14 Department of Movement Disorders and Neurology, INSERM, CIC04, CHU Nantes, Nantes, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Giordana</LastName><ForeName>Caroline</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>15 Department of Movement Disorders and Neurology, CHU Nice, Nice, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Drapier</LastName><ForeName>Sophie</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>16 Department of Neurology, EA- 425 Université Rennes 1 et CHU Pontchaillou, CHU Rennes, Rennes, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Maltête</LastName><ForeName>David</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>17 Department of Neurology and INSERM CIC-CRB 0204, Rouen University Hospital, CHU Rouen Rouen, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tranchant</LastName><ForeName>Christine</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>12 Department of Movement Disorders and Neurology, CHU Strasbourg, Strasbourg, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Houeto</LastName><ForeName>Jean-Luc</ForeName><Initials>JL</Initials><AffiliationInfo><Affiliation>11 Department of Movement Disorders and Neurology, Centre d'Investigation Clinique, INSERM CIC 0802, INSERM U1084, Laboratoire de Neurosciences Expérimentales et Cliniques, CHU de Poitiers, Poitiers, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Debû</LastName><ForeName>Bettina</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>10 Department of Psychiatry and Neurology, CHU Grenoble, Grenoble, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Azulay</LastName><ForeName>Jean-Philippe</ForeName><Initials>JP</Initials><AffiliationInfo><Affiliation>9 Department of Neurology and Movement Disorders - APHM Timone University Hospital and Institut de Neurosciences de la Timone, AMU-CNRS UMR 7289, Marseille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tison</LastName><ForeName>François</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>8 Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR CNRS 5293 and CHU de Bordeaux, Bordeaux, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Destée</LastName><ForeName>Alain</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>1 Department of Movement Disorders and Neurology, Lille University, CHU Lille, Lille, France 18 INSERM U837/6 Lille JPARC, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vidailhet</LastName><ForeName>Marie</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>6 Department of Nuclear Medicine, Lille University, CHU Lille, Lille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rascol</LastName><ForeName>Olivier</ForeName><Initials>O</Initials><AffiliationInfo><Affiliation>7 Departments of Clinical Pharmacology and Neurosciences, CIC9302, University Hospital and Paul Sabatier University, Toulouse, France 19 INSERM NS-PARK National Network, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dujardin</LastName><ForeName>Kathy</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>1 Department of Movement Disorders and Neurology, Lille University, CHU Lille, Lille, France 2 INSERM U1171, Lille University, Lille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Defebvre</LastName><ForeName>Luc</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>1 Department of Movement Disorders and Neurology, Lille University, CHU Lille, Lille, France 2 INSERM U1171, Lille University, Lille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bordet</LastName><ForeName>Régis</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>2 INSERM U1171, Lille University, Lille, France 18 INSERM U837/6 Lille JPARC, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sablonnière</LastName><ForeName>Bernard</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>3 Department of Molecular Biology and Pathology Centre, Lille University, CHU Lille, Lille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Devos</LastName><ForeName>David</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>1 Department of Movement Disorders and Neurology, Lille University, CHU Lille, Lille, France 2 INSERM U1171, Lille University, Lille, France 20 Department of Medical Pharmacology, Lille University, CHU Lille, Lille, France david.devos@chru-lille.fr.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><CollectiveName>Parkgait-II Study Group</CollectiveName></Author></AuthorList><Language>eng</Language><DataBankList CompleteYN="Y"><DataBank><DataBankName>ClinicalTrials.gov</DataBankName><AccessionNumberList><AccessionNumber>NCT00914095</AccessionNumber></AccessionNumberList></DataBank></DataBankList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016448">Multicenter Study</PublicationType><PublicationType UI="D016449">Randomized Controlled Trial</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2015</Year><Month>03</Month><Day>23</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Brain</MedlineTA><NlmUniqueID>0372537</NlmUniqueID><ISSNLinking>0006-8950</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D050483">Dopamine Plasma Membrane Transport Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C493214">SLC6A3 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>46627O600J</RegistryNumber><NameOfSubstance UI="D007980">Levodopa</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.1.1.6</RegistryNumber><NameOfSubstance UI="D002394">Catechol O-Methyltransferase</NameOfSubstance></Chemical><Chemical><RegistryNumber>VTD58H1Z2X</RegistryNumber><NameOfSubstance UI="D004298">Dopamine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>AIM</CitationSubset><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002394" MajorTopicYN="N">Catechol O-Methyltransferase</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004298" MajorTopicYN="N">Dopamine</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D050483" MajorTopicYN="N">Dopamine Plasma Membrane Transport Proteins</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004311" MajorTopicYN="N">Double-Blind Method</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020022" MajorTopicYN="N">Genetic Predisposition to Disease</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005838" MajorTopicYN="N">Genotype</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007980" MajorTopicYN="N">Levodopa</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle 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