Effect of Val92Met and Arg163Gln variants of the MC1R gene on freckles and solar lentigines in Japanese.

Melanocortin-1 receptor (MC1R) is a highly polymorphic gene. The variety of the variants is dependent on the ethnic background of the individual. In Caucasians, specific variants, such as Arg151Cys, Arg160Trp, and Asp294His, are strongly associated with red hair, skin cancer and pigmented lesions. In Asians, there is no report so far indicating an association such as that observed in Caucasians. Here, we performed an association study on melanogenic phenotypes in 245 Japanese individuals. We focused on freckles and solar lentigines as melanogenic phenotypes. The 92Met allele and the 163Arg allele were positively associated with freckles and severe solar lentigines; the 163Gln allele showed a negative association. Those subjects who were homozygous for both the 92Met and 163Arg alleles had a highly elevated risk of developing freckles (OR: 7.92; 95% CI: 1.52-39.6) and severe solar lentigines (OR: 4.08; 95% CI: 1.34-13.1). Our study is the first report to show a clear association of MC1R variants on melanogenic phenotypes in Asians and also indicates the importance of Arg163Gln. In vitro studies by other groups demonstrated that Val92Met impaired MC1R function but Arg163Gln did not. Based on these in vitro studies, we believe that the result we observed for Val92Met could be attributed to impaired MC1R function, while, for Arg163Gln, other factors, e.g. effect of other loci, need to be considered.