The MC1R melanoma risk variant p.R160W is associated with Parkinson disease

Abstract

Epidemiological studies have reported the co-occurrence of Parkinson disease (PD) and melanoma. Common genetic variants in the MC1R (melanocortin 1 receptor) gene, which determines skin and hair color, are associated with melanoma. Here we investigated whether genetic variants in MC1R modulate the risk of PD by sequencing the entire gene in 870 PD patients and 736 controls ascertained from Spain. We found that the MC1R variant p.R160W (rs1805008) is marginally associated with PD (odds ratio = 2.10, gender- and age-adjusted p = 0.009, Bonferroni-corrected p = 0.063). Our results suggest that MC1R genetic variants modulate the risk of PD disease in the Spanish population.

A Common Variant in the MC1R Gene (p.V92M) is associated with Alzheimer’s Disease Risk

“…The major one being sample size, which is not large enough to provide reliable evidence for a genetic AD risk factor, especially if we focus on the controls size (N = 160) which is small. However, our work provides positive results from our hypothesis and highlights a putative role of the MC1R gene in the genetic susceptibility to developing neurodegenerative diseases, which is in the same line as previously published works [22,23].…”

“…Functional studies of MC1R variants conducted in melanocytes, reveal that certain variants reduce cell surface protein expression and diminished capacity to stimulate cAMP, resulting in the red hair color phenotype [17]. Interestingly, two MC1R variants related to red hair color phenotype modulate the risk to develop PD [22,29]. These findings partially explain the previous epidemiological evidence describing a bidirectional link between PD and CM [21].…”

“…All variants were in Hardy-Weinberg equilibrium within both the control population and LOAD patients (allelic and genotypic frequencies are listed in Table 3). Moreover, frequencies of MC1R variants observed in control subjects were compared with those observed in other set of controls (N = 736) free from neurodegenerative disorders used in other study [29]. No statistical significant differences were observed between both groups.…”

“…It has been established that several MC1R polymorphisms constitute a risk factor to develop skin cancer (melanoma and non-melanoma skin cancer) [18,19], in part, by promoting an increased oxidative stress in skin cells [20]. Notably, co-occurrence of Parkinson's disease (PD) and cutaneous melanoma (CM) has been reported in epidemiological studies [21] and previous evidence indicates that MC1R is involved in the bidirectional link between both diseases [22,23]. Thus, we hypothesized that certain MC1R variants may increase the oxidative damage and/or deregulate inflammatory processes in brain cells, which consequently, increase the susceptibility of developing other neurodegenerative disorders beyond PD.…”

Rare variants in MC1R/TUBB3 exon 1 are not associated with Parkinson's disease

“…Tell-Marti and colleagues recently published a variant (rs1805008; p.R160W) in the melanocortin 1 receptor ( MC1R ) gene associated with an increased risk of Parkinson’s disease (PD) in a Spanish series 1 . According to ExAC Browser (http://exac.broadinstitute.org/) this variant is a common variant in non-Finnish Europeans (Minor allele frequency; MAF = 0.08) and it may help explain the previous associations establishing that PD patients have an increased risk of developing melanoma 2 .…”