Assessment Of Single Nucleotide Polymorphisms Of Melanocortin-1 Receptor (MC1R) Genes In Vitiligo Patients

With the completion of the human genome project, attention is now rapidly shifting towards the study of individual genetic variation. The most abundant source of genetic variation in the human genome is represented by single nucleotide polymorphisms (SNPs), which can account for heritable inter individual differences in complex phenotypes. Identification of SNPs that contribute to susceptibility to complex diseases will provide highly accurate diagnostic information that will facilitate early diagnosis, prevention, and treatment of human diseases.Vitiligo vulgaris (VV) is an acquired, non-contagious disorder in which progressive, patchy loss of pigmentation of skin and often overlying hair, and mucous membranes. Known for thousands of years because of its visually evident phenotype, vitiligo is the most common pigmentary disorder. Vitiligo was seen as a complex disorder which involved a combination of a lot of genes and environment factors. The menalocyte loss of the involved areas was considered. So, the hypotheses was suggest that the pathogenesis of vitiligo should link with the menalocyte's biochemical function. Melanocortin-1 receptor (MC1R),a gene coding special receptor of menalocytes, was confirmed to be related with many pigmentary disorders and melanoma. It was a key gene of many menalocyte disorders. So we presume that the SNPs of MC1R should be correlated with the pathogenesis of vitiligo.To assess the possible relationship between MC1R and the pathogenesis of vitiligo vulgaris. 365 patients were recruited. Questionnaires which included the clinical characters were completed. Among them, 48 cases(13.15%) have positive family history. It is said that the pathogenesis of vitiligo may have relationship with genetics. The MC1Rs'coding regions of 40 vitiligo vulgaris patients (disease group) and 38 medical examination persons (control group) were directly sequenced. Latest SNP data of Asian people's MC1R on the NCBI was collected as literature group (85 Asian controls detected by Rana etc).χ~2 analysis was used to assess the frequencies of the SNP of the MC1R among the disease group, control group and literature group.The main results and conclusions were summarized as follows:1. There were 193 males (52.88%) and 172 females (47.12%) enrolled. 48 persons have family history(13.15%). The predilection site of lesions were face, chest-back, extremity and mucous membrane in turn. The area of lesions is main among 1%to 5% of the surface area. Males'lesions are often more serious than females'. 82 cases (22.47%) have causative factors. Nervousness and depression are common.2. Both in disease group and control group, five MC1R coding region single nucleotide polymorphisms (SNPs) were founded: G274A (Val92Met), T359C (His120His), G488A (Gln163Arg), C491A(Ala164Gln) and A942G(Thr312Thr). Among them, G274A (Val92Met) and G488A(Gln163Arg)had much higher frequencies. G274A(Val92Met) was 26.25% in patient group versus 22.37% in control group, and G488A(Gln163Arg) was 81.25% in patient group versus 57.89% in control group. Significant difference was found in Gln163Arg between disease group and control group(χ~2=9.966,P<0.01). The difference between disease group and control group was also significant(χ~2=6.214,P<0.05). But no significant difference existed between literature group and control group(P>0.05). And no significant difference of frequencies of the allele G274A (Val92Met) existed in the three groups(P>0.05). A novel variant allel, C491A(Ala164Gln), was found.In conclusion:1. Result of vitiligo clinical analysis. Male vitiligos vulgaris in our recruited patients are often more serious than females in lesion. The pathogenesis of vitiligo vulgaris may be relationship with genetics. Emotion and intension may bring about the onset of vitiligo vulgaris.2. Result of MC1R's SNPs. There exist association between the polymorphism of MC1R Gln163Arg and pathogenesis of vitiligo, whereas no correlation exist between G274A (Val92Met) and the pathogenesis of vitiligo. A novel allel, C491A(Ala164Gln), was found in our study.