Show simple item record

dc.contributor.authorKlebe, Stephan
dc.contributor.authorGolmard, Jean-Louis
dc.contributor.authorNalls, Michael A
dc.contributor.authorSaad, Mohamad
dc.contributor.authorSingleton, Andrew B
dc.contributor.authorBras, Jose M
dc.contributor.authorHardy, John
dc.contributor.authorSimon-Sanchez, Javier
dc.contributor.authorHeutink, Peter
dc.contributor.authorKuhlenbäumer, Gregor
dc.contributor.authorCharfi, Rim
dc.contributor.authorKlein, Christine
dc.contributor.authorHagenah, Johann
dc.contributor.authorGasser, Thomas
dc.contributor.authorWurster, Isabel
dc.contributor.authorLesage, Suzanne
dc.contributor.authorLorenz, Delia
dc.contributor.authorDeuschl, Günther
dc.contributor.authorDurif, Franck
dc.contributor.authorPollak, Pierre
dc.contributor.authorDamier, Philippe
dc.contributor.authorTison, François
dc.contributor.authorDurr, Alexandra
dc.contributor.authorAmouyel, Philippe
dc.contributor.authorLambert, Jean-Charles
dc.contributor.authorTzourio, Christophe
dc.contributor.authorMaubaret, Cécilia
dc.contributor.authorCharbonnier-Beaupel, Fanny
dc.contributor.authorTahiri, Khadija
dc.contributor.authorVidailhet, Marie
dc.contributor.authorMartinez, Maria
dc.contributor.authorBrice, Alexis
dc.contributor.authorCorvol, Jean-Christophe
dc.date.accessioned2014-08-18T09:59:22Z
dc.date.available2014-08-18T09:59:22Z
dc.date.issued2013-06
dc.date.submitted2013
dc.identifier.citationJ. Neurol. Neurosurg. Psychiatr. 2013, 84 (6):666-73en
dc.identifier.issn1468-330X
dc.identifier.pmid23408064
dc.identifier.doi10.1136/jnnp-2012-304475
dc.identifier.urihttp://hdl.handle.net/2336/324900
dc.descriptionTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.en
dc.description.abstractThe catechol-O-methyltranferase (COMT) is one of the main enzymes that metabolise dopamine in the brain. The Val158Met polymorphism in the COMT gene (rs4680) 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 rs4680 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 COMT genotype and gender considered as fixed effects and cohort and cohort-gender interaction as random effects. COMT 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.
dc.language.isoenen
dc.publisherBMJ Publishing Groupen
dc.relation.urlhttp://dx.doi.org/10.1136/jnnp-2012-304475en
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646288/en
dc.rightsArchived with thanks to Journal of neurology, neurosurgery, and psychiatryen
dc.subjectParkinsonsveikien
dc.subjectAldraðiren
dc.subjectArfgengien
dc.subject.meshAge of Onseten
dc.subject.meshAgeden
dc.subject.meshCatechol O-Methyltransferaseen
dc.subject.meshGenotypeen
dc.subject.meshHumansen
dc.subject.meshMaleen
dc.subject.meshMiddle Ageden
dc.subject.meshParkinson Diseaseen
dc.subject.meshPolymorphism, Single Nucleotideen
dc.subject.meshSex Factorsen
dc.titleThe Val158Met COMT polymorphism is a modifier of the age at onset in Parkinson's disease with a sexual dimorphism.en
dc.typeArticleen
dc.contributor.departmentINSERM, UMR S975, CR ICM, Paris, France, UPMC Univ Paris 06, UMR S975, CR ICM, Pitie Salpetriere Hosp, Paris, France, Hop La Pitie Salpetriere, CR ICM, CNRS, UMR 7225, Paris, France, Hop La Pitie Salpetriere, AP HP, Dept Genet & Cytogenet, F-75651 Paris 13, France, Hop La Pitie Salpetriere, INSERM, CIC 9503, F-75651 Paris 13, France, Hop La Pitie Salpetriere, AP HP, Dept Neurol, F-75651 Paris 13, France, Univ Hosp Wurzburg, Dept Neurol, Wurzburg, Germany, Hop La Pitie Salpetriere, AP HP, Dept Biostat, F-75651 Paris 13, France, NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA, CPTP, INSERM U1043, Toulouse, France, Univ Toulouse 3, F-31062 Toulouse, France, UCL Inst Neurol, Dept Mol Neurosci, London, England, Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Sect Med Gen, Amsterdam, Netherlands, Univ Kiel, Inst Expt Med, Kiel, Germany, Hop La Pitie Salpetriere, AP HP, Dept Pharmacol, F-75651 Paris 13, France, Univ Tunis El Manar, Fac Med Tunis, Ctr Natl Pharmacovigilance Tunis, Serv Pharmacol Clin, Tunis, Tunisia, Univ Lubeck, Inst Neurogenet, Lubeck, Germany, Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurodegenerat Dis, Tubingen, Germany, German Ctr Neurodegenerat Dis DZNE, Dept Neurodegenerat Dis, Tubingen, Germany, Univ Kiel, UKS H, Dept Neurol, Kiel, Germany, CHU Grenoble, Hop Gabriel Montpied, Dept Neurol, Clermont Ferrand, France, CHU Grenoble, Dept Neurol, Grenoble, France, CHU Nantes, Ctr Invest Clin, F-44035 Nantes 01, France, Hop Haut Leveque, Dept Neurol, Pessac, France, INSERM, U744, F-59045 Lille, France, Inst Pasteur, Lille, France, Univ Lille Nord France, Lille, France, Univ Paris 06, Hop Pitie Salpetriere, Modelisat Rech Clin ER4 UPMC, CNRS CRICM 7225, Paris, France, INSERM UMR S708, Paris, France, Univ Bordeaux Segalen, INSERM U897, Bordeaux, France, INSERM, UMR S975, Paris, Franceen
dc.identifier.journalJournal of neurology, neurosurgery, and psychiatryen
dc.rights.accessOpen Access - Opinn aðganguren
refterms.dateFOA2018-09-12T13:30:51Z
html.description.abstractThe catechol-O-methyltranferase (COMT) is one of the main enzymes that metabolise dopamine in the brain. The Val158Met polymorphism in the COMT gene (rs4680) 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 rs4680 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 COMT genotype and gender considered as fixed effects and cohort and cohort-gender interaction as random effects. COMT 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.


Files in this item

Thumbnail
Name:
J Neurol Neurosurg Psychiatry- ...
Size:
212.1Kb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record