The role of the melanoma gene MC1R in Parkinson disease and REM sleep behavior disorder

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.

Red hair, MC1R variants, and risk for Parkinson's disease – a meta‐analysis

“…A). When we further examined two MC1R red hair color alleles, we found that p.R151C variant was associated with marginally increased risk of PD (pooled OR = 1.101; 95% CI: 1.002, 1.210; P = 0.046; PD case number = 8454] (Fig. B).…”

“…We identified six publications based on eight study cohorts in total from 2009 to 2016, all with study focus on hair color or MC1R p.R151C or p.R160W polymorphisms (Table ) . PD cases were of US, French/French‐Canadian, UK, German, Greek, Dutch, and Spanish origins, overall representing white populations . PD diagnosis was generally ascertained by a neurologist or clinician according to the United Kingdom Parkinson's Disease Society Brain Bank Criteria.…”

“…In a case–control study based on 870 PD cases in Spain, another red hair‐associated MC1R variant p.R160W (rs1805008) was found to be associated with higher PD risk . However, other epidemiological studies on this topic did not support an MC1R ‐PD link . In this report, we searched all literature indexed in PubMed and performed meta‐analyses of studies that examined the association between red hair color, MC1R p.R151C or p.R160W, two most studied MC1R loss‐of‐function polymorphisms, and PD risk.…”

“…Our initial investigation based on more than 120,000 US men and women demonstrated that red hair color and red hair‐associated MC1R p.R151C polymorphism (rs1805007) were associated with higher risk of PD . MC1R variants have since garnered considerable interest and debate over their significance in the PD and melanoma association . In a case–control study based on 870 PD cases in Spain, another red hair‐associated MC1R variant p.R160W (rs1805008) was found to be associated with higher PD risk .…”

The melanoma‐linked “redhead” MC1R influences dopaminergic neuron survival

“…15 The association was substantiated by another study linking PD with an alternative red hair MC1R variant in an independent cohort. 16 Although other studies [17][18][19][20] did not replicate a significant MC1R-PD association, which may be attributable to technical or population differences across studies, 21 MC1R has nevertheless emerged as having a potential role at the interface of melanoma and PD.…”