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Klebe, S.* ; Golmard, J.L.* ; Nalls, M.A.* ; Saad, M.* ; Singleton, A.B.* ; Bras, J.M.* ; Hardy, J.* ; Simon-Sanchez, J.* ; Heutink, P.* ; Kuhlenbäumer, G.* ; Charfi, R.* ; Klein, C.* ; Hagenah, J.* ; Gasser, T.* ; Wurster, I.* ; Lesage, S.* ; Lorenz, D.* ; Deuschl, G.* ; Durif, F.* ; Pollak, P.* ; Damier, P.* ; Tison, F.* ; Dürr, A.* ; Amouyel, P.* ; Lambert, J.C.* ; Tzourio, C.* ; Maubaret, C.* ; Charbonnier-Beaupel, F.* ; Tahiri, K.* ; Vidailhet, M.* ; Martinez, M.* ; Brice, A.* ; Corvol, J.C.* ; French Parkinson's Disease Genetics Study Group (*) ; International Parkinson's Disease Genomics Consortium (IPDGC) (Illig, T. ; Lichtner, P.)

The Val158Met COMT polymorphism is a modifier of the age at onset in Parkinson's disease with a sexual dimorphism.

J. Neurol. Neurosurg. Psychiatr. 84, 666-673 (2013)
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The 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Movement Disorders; Neurogenetics; Parkinson's Disease
Sprache englisch
Veröffentlichungsjahr 2013
HGF-Berichtsjahr 2013
ISSN (print) / ISBN 0022-3050
e-ISSN 1468-330X
Zeitschrift Journal of Neurology, Neurosurgery, and Psychiatry
Quellenangaben Band: 84, Heft: 6, Seiten: 666-673 Artikelnummer: , Supplement: ,
Verlag BMJ Publishing Group
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Molecular Epidemiology (AME)
Institute of Human Genetics (IHG)
POF Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-504200-001
G-500700-001
PubMed ID 23408064
DOI 10.1136/jnnp-2012-304475
Scopus ID 84877634080
Erfassungsdatum 2013-07-04
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