Association Study On Polymorphisms Of MC1R Gene And Phenotypic Characteristics Such As Skin Colour In A Chinese Han Population

Melanocortin-1 receptor (MCIR) is a kind of G-protein coupled receptor. The main function of MC1R is responsible for melanin production pathway, which converts eumelanin into pheomelanin. When the receptor is activated by the a-melanocyte stimulating hormone (a-MSH), adenylyl cyclase will be regulated and the level of cAMP will be raised, which further activates the Tyrosinase, eventually the pheomelanin will be produced. However, as the antagonistic substances of a-MSH, Agouti Signaling protein (ASIP) can competitively bind with MCIR. If the melanin production pathway is completely blocked or the binding of a-MSH with MCIR is suppressed, the final product of this pathway will be eumelanin rather than pheomelanin.The MCIR protein contains 377 Amino acids. It has been proved to be a highly polymorphic gene. According to the SNP database of NCBI (National Center for Biotechnology Information), there are 28 SNP sites in the coding region of this gene, and most of the SNP are associated with red hair and/or fair skin. What's more, many studies about this gene have indicated that mutations of this gene are associated with the sensitivity of skin to sun and the number of freckle, and even the risk of skin cancer will be raised.Doing association study of the polymorphisms in MCIR and the skin phenotypic characteristics like skin colour in Chinese Han population is not only important but very necessary. In order to investigate the relationship between the polymorphisms of MCIR gene and the skin phenotypes of Chinese Han, a population of 139 Han individuals who were skin healthy was analyzed. As a result,7 polymorphism sites (SNP200, SNP274, SNP359, SNP421, SNP488, SNP497 and SNP942) were investigated in the coding region of MCIR gene. Of the 7 sites, SNP421 and SNP497 were the first time to report in Chinese Han population. By analyzing the relevance between the 4 SNP sites (SNP274, SNP359, SNP488 and SNP942) which had relatively high minor allele frequency and the skin phenotypes, SNP274 was found to be significantly correlated with skin colour and freckles conditions. The homozygous mutant genotype AA had strong association with light skin color (OR=3.828, 95% CI:1.117-13.116). And the mutant heterozygous genotype GA was associated with less number of freckles (OR=2.255,95% CI:1.094-4.650). For SNP488, its mutant heterozygous genotype AG was strongly associated with darker hair colour (OR=2.676,95% CI: 1.006-7.120). SNP942 was also found to have association with skin colour, its mutant homozygous genotype GG associated with light skin colour with OR as high as 5.850 (95% CI:1.176-29.103).In all, this work indicated that variations in MC1R gene indeed have some relation with skin phenotypic characteristics in Chinese Han population. Such meaningful validating work is the first time both in Chinese Han population and in Asian Yellow population. It will provide theoretical support for skin melanoma research as well as cosmetology study and help to predict and select the person's skin colour.