The role of the melanoma gene MC1R in Parkinson disease and REM sleep Behavior Disorder

• Published in: Neurobiology of aging Vol. 43; pp. 180.e7 - 180.e13
• Main Authors: Gan-Or, Ziv, Mohsin, Noreen, Girard, Simon L, Montplaisir, Jacques Y, Ambalavanan, Amirthagowri, Strong, Stephanie, Mallett, Victoria, Laurent, Sandra B, Bourassa, Cynthia V, Boivin, Michel, Langlois, Melanie, Arnulf, Isabelle, Högl, Birgit, Frauscher, Birgit, Monaca, Christelle, Desautels, Alex, Gagnon, Jean-François, Postuma, Ronald B, Dion, Patrick A, Dauvilliers, Yves, Dupre, Nicolas, Alcalay, Roy N, Rouleau, Guy A
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-07-2016; Elsevier
• Subjects: Adult; Aged; Female; Genetic Association Studies; Genetic Predisposition to Disease - genetics; Genetic Variation; Genetics; Geriatry and gerontology; Human health and pathology; Humans; Internal Medicine; Life Sciences; Male; MC1R; Melanoma; Melanoma - genetics; Middle Aged; Neurology; Neurons and Cognition; Parkinson disease; Parkinson Disease - genetics; Receptor, Melanocortin, Type 1 - genetics; REM Sleep Behavior Disorder - genetics; Young Adult; Parkinson disease; Genetics; melanoma; MC1R; Melanoma
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2016.03.029

Abstract The MC1R gene, suggested to be involved in Parkinson disease (PD) and melanoma, was sequenced in PD patients (n=539) and controls (n=265) from New-York, and PD patients (n=551), rapid eye movement sleep behavior disorder (RBD) patients (n=351) and controls (n=956) of European ancestry. Sixty-eight MC1R variants were identified, including 7 common variants with frequency>0.01. None of the common variants was associated with PD or RBD in the different regression models. In a meta-analysis with fixed-effect model, the p.R160W variant was associated with an increased risk for PD (OR=1.22, 95%CI 1.02-1.47, p =0.03) but with significant heterogeneity ( p =0.048). Removing one study that introduced the heterogeneity resulted in non-significant association (OR=1.11, 95%CI 0.92-1.35, p =0.27, heterogeneity p =0.57). Rare variants had similar frequencies in patients and controls (10.54% and 10.15%, respectively, p =0.75), and no cumulative effect of carrying more than one MC1R variant was found. The current study does not support a role for the MC1R p.R160W and other variants in susceptibility for PD or RBD.