• J. Neurol. Neurosurg. Psychiatr. · Jun 2013

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

    • Stephan Klebe, Jean-Louis Golmard, Michael A Nalls, Mohamad Saad, Andrew B Singleton, Jose M Bras, John Hardy, Javier Simon-Sanchez, Peter Heutink, Gregor Kuhlenbäumer, Rim Charfi, Christine Klein, Johann Hagenah, Thomas Gasser, Isabel Wurster, Suzanne Lesage, Delia Lorenz, Günther Deuschl, Franck Durif, Pierre Pollak, Philippe Damier, François Tison, Alexandra Durr, Philippe Amouyel, Jean-Charles Lambert, Christophe Tzourio, Cécilia Maubaret, Fanny Charbonnier-Beaupel, Khadija Tahiri, Marie Vidailhet, Maria Martinez, Alexis Brice, Jean-Christophe Corvol, French Parkinson's Disease Genetics Study Group, and International Parkinson's Disease Genomics Consortium (IPDGC).
    • 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.
    • J. Neurol. Neurosurg. Psychiatr. 2013 Jun 1; 84 (6): 666673666-73.

    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.

      Pubmed     Free full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…