Correlation Of A Single Nucleotide Polymorphism Of Rs9468925 MHC Region With Phenotypes Of Generalized Vitiligo In Chinese Population

Background Vitiligo might follow a pattern of polygenetic or multifactorial inheritance in different geographical regions and ethnic groups.Vitiligo is one of common diseases in dermatology, and several hypotheses have been proposed to explain the pathogenesis of vitiligo. Several hypotheses have been proposed to explain the pathogenesis of vitiligo, including self-destructive, biochemical, neural, autoimmune and genetic hypotheses, but each of them can explain only a small proportion of cases.In the past few years, many susceptibility genes of vitiligo had revealed through linkage analysis, candidate gene. Now in our previous GWAS in the Chinese Han population, we identified two independent association signals within the major histocompatibility complex (MHC) region (rs1111966200, rs9468925). Further analyses suggested that the strong association at rs1111966200 might reflect the reported association of the HLA-A*3001, HLA-B*1302, HLA-C*0602 and HLA-DRB1*0701 alleles and that the association at rs9468925 might represent a previously unknown HLA susceptibility allele. We also identified one previously undescribed risk locus at 6q27 which contains three genes: RNASET2, FGFR1OP and CCR6. We extracted the data of MHC region from vitiligo GWA study results and investigated the association between rs9468925 polymorphism of MHC region and vitiligo penotypes in Chinese Han population.Objective To investigate the association between a single nucleotide polymorphism of rs9468925 within MHC region and phenotypes of vitiligo in Chinese Han population. Methods Based on stratifying analysis of the age of onset, familial history, halo nevi involvement, and clinical types, the study compared the genotype and allele frequency distribution of rs9468925 polymorphism within MHC region with some phenotypes of vitiligo vulgaris in the Han Chinese population in order to further explore the genetics pathogenesis.Results 1.The genotype frequency of rs9468925 polymorphism within MHC region was of statistical significance between the cases and the controls(χ²=138.4, df=2, P=8.85×10^-31), there was a similar trend for the allelic frequency(χ²=136.49, df=1,P=1.56×10^-31, OR= 0.73, 95%CI:0.69-0.77).2.The genotype and allelic frequencies of rs9468925 polymorphism were statistical significance between the≤20 years age of onset cases and controls(χ²=140.93, df=, P=2.50×10^-31;χ²=140.42, df=1, P=2.16×10^-32, OR=0.68, 95%CI: 0.63-0.72). The genotype and allelic frequencies of rs9468925 polymorphism were also statistical significance between the >20 years age of onset cases and controls(χ²=43.87, df=2, P=2.97×10^-10;χ²=43.23, df=1, P=4.87×10^-11, OR=0.80, 95%CI:0.74-0.85). However,there were also statistical significance between the≤20 years age of onset and>20 years age of onset cases(χ²=16.53, df=2, P=2.57×10^-4;χ²=16, df=1, P=6.01×10^-5, OR= 0.80, 95%CI: 0.74-0.85). 3.The genotype and allelic frequencies of rs9468925 polymorphism within MHC region were statistical significance between the involved body surface area <5% cases and controls(χ²=109.4, df=2, P=1.72×10^-24;χ²=109.67, df=1, P=1.16×10^-25, OR= 0.73, 95%CI:0.69-0.77). The genotype and allelic frequencies of rs9468925 polymorphism within MHC region were statistical significance between the involved body surface area≥5% cases and controls(χ²=63.79, df=2, P=1.41×10^-14;χ²=58.71, df=1, P=1.83×10^-14, OR=0.72, 95%CI: 0.66-0.78). And there were also statistical significance between the involved <5% and≥5% body surface area cases in the genotype frequencies (χ²=7.39, df=2, P=0.025), but no significance in allelic frequencies (χ²=0.3, df=1, P=0.58, OR=1.03, 95%CI:0.94-1.12).4.The genotype and allelic frequencies of rs9468925 polymorphism within MHC region were statistical significance between the familial cases and controls(χ²=34.97, df=2, P=2.55×10^-8;χ²=32.92, df=1, P=9.59×10^-9, OR= 0.70,95%CI:0.63-0.79).The genotype and allelic frequencies of rs9468925 polymorphism were also statistical significance between the sporadic cases and controls(χ²=63.79, df=2, P=1.41×10^-14;χ²=58.71, df=1, P=1.83×10^-14, OR= 0.72,95%CI:0.66-0.78). However, there weren't statistical significance between the familial and sporadic cases(χ²=3.28, df=2, P=0.19;χ²=0.38, df=1, P=0.54, OR =0.96,95%CI: 0.85-1.09).5. The genotype and allelic frequencies of rs9468925 polymorphism within MHC region were statistical significance between the involved positive autoimmune disease cases and controls (χ²=14.23, df=2, P=0.001;χ²=13.94, df=1, P=1.88×10^-4, OR=0.72, 95%CI: 0.60-0.85). The genotype and allelic frequencies of rs9468925 polymorphism within MHC gene were statistical significance between the involved negative autoimmune disease cases and controls (χ²=132.93, df=2, P=1.36×10^-29;χ²=131.18, df=1, P=1.93×10^-30, OR= 0.73, 95%CI:0.69-0.77). However, there weren't statistical significance between the involved positive and negative autoimmune disease cases(χ²=0.43, df=2,P=0.81;χ²=0.57, df=1, P=0.45, OR=1.09, 95%CI: 0.87-1.37). 6.The genotype and allelic frequencies of rs9468925 polymorphism within MHC region were statistical significance between focal cases and controls(χ²=38.04, df=2, P=5.48×10^-9;χ²=37.06, df=1, P=1.14×10^-9, OR=0.79, 95%CI: 0.73-0.85). The genotype and allelic frequencies of rs9468925 polymorphism were also statistical significance between the vitiligo vulgaris cases and controls(χ²=121.83, df=2, P=3.51×10^-27;χ²=119.87, df=1, P=6.76×10^-28, OR= 0.70, 95%CI: 0.66-0.75). The genotype and allelic frequencies of rs9468925 polymorphism within MHC region were statistical significance between universal vitiligo cases and controls(χ²=14.41, df=2, P=0.001;χ²=13.31, df=1, P=2.64×10^-4, OR=0.79, 95%CI: 0.73-0.85) .The genotype and allelic frequencies of rs9468925 polymorphism within MHC region were statistical significance between acrofacial vitiligo cases and controls (χ²=17.00, df=2, P=2.04×10^-4;χ²=16.05, df=1, P=6.17×10^-5, OR=0.72, 95%CI: 0.62-0.85). However, there were statistical significance among cases in the genotype frequencies (χ²=13.98, df=6, P=0.03), but no significance in allelic frequencies(χ²=6.74, df=3, P=0.08).Conclusion 1. The rs9468925 polymorphism within MHC region is associated with the susceptibility of generalized vitiligo in the Han Chinese population. 2. The rs9468925 polymorphism within MHC region is associated with age of onset of generalized vitiligo. 3. The rs9468925 polymorphism within MHC region is associated with the involved basic surface area. 4. The rs9468925 polymorphism within MHC is associated with clinical type of generalized vitiligo. 5. Our findings indicated that the rs9468925 polymorphism within MHC region may have no effected on family history, the involved autoimmune disease which maybe associate with different vitiligo genetic basis and pathogenesis.