VARIANTS OF THE MELANOCYTE-STIMULATING HORMONE-RECEPTOR GENE ARE ASSOCIATED WITH RED HAIR AND FAIR SKIN IN HUMANS

Melanin pigmentation protects the skin from the damaging effects of ul traviolet radiation (UVR). There are two types of melanin, the red pha eomelanin and the black eumelanin, both of which are present in human skin(1). Eumelanin is photoprotective whereas phaeomelanin, because of its potential to generate free radicals in response to UVR(2), may co ntribute to UV-induced skin damage. Individuals with red hair have a p redominance of phaeomelain in hair and skin and/or a reduced ability t o produce eumelanin, which may explain why they fail to tan and are at risk from UVR(1). In mammals the relative proportions of phaeomelanin and eumelanin are regulated by melanocyte stimulating hormone (MSH), which acts via its receptor (MC1R), on melanocytes, to increase the sy nthesis of eumelanin(3,4) and the product of the agouti locus which an tagonises this action(5). In mice, mutations at either the MC1R gene o r agouti affect the pattern of melanogenesis resulting in changes in c oat colour(6,7). We now report the presence of MC1R gene sequence vari ants in humans. These were found in over 80% of individuals with red h air and/or fair skin that tans poorly but in fewer than 20% of individ uals with brown or black hair and in less than 4% of those who showed a good tanning response. Our findings suggest that in humans, as in ot her mammals, the MC1R is a control point in the regulation of pigmenta tion phenotype and, more importantly, that variations in this protein are associated with a poor tanning response.