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Correlation of A Single Nucleotide Polymorphism of rs9468925 MHC Region with Phenotypes of Generalized Vitiligo in Chinese Population

Author: LiuJianLan
Tutor: ZhangXueJun;YangSen
School: Anhui Medical University,
Course: Dermatology and Venereology
Keywords: Vitiligo MHC Single nucleotide polymorphisms
CLC: R758.41
Type: Master's thesis
Year: 2011
Downloads: 23
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Abstract


Background vitiligo (OMIM, # 193200) is a polygenic disease, because of different races in different regions show different prevalence [2-4]. Vitiligo is a common the hypopigmented skin disease mainly affects the skin and hair of unknown pathogenesis of complex diseases. Its pathogenesis has not yet been fully elucidated, the current mechanisms include genetics, autoimmune theory, melanocytes destroy the doctrine, the neurochemical factor theory, but no conclusive. Genetic factors play an important role in the pathogenesis of vitiligo. Past vitiligo susceptibility genes through linkage analysis and candidate gene approach. Now we found through genome-wide association study found two independent association signals in the MHC region mutation sites (rs11966200, rs9468925) Further studies showed that rs1196200 may be associated with the HLA-A * 3001, HLA-B * 1302, of HLA- C * 0602, as well as HLA-DRB1 * 0701 allele associated rs9468925 might represent a previously unknown susceptibility genes. Also discovered a previously undescribed risk locus in 6q27 (rs2236313), and contains three the gene RNASET2, FGFR1OP and CCR6 here. To investigate whether the SNP loci vitiligo phenotypes related with the Han people, the research and application research group vitiligo susceptibility genes GWA study results analysis the MHC region single nucleotide polymorphisms SNPrs9468925 and Han people with vitiligo vulgaris phenotype relationship. Purpose on the age of onset of vitiligo vulgaris area of ??onset, family history, associated with autoimmune diseases and clinical type stratified analysis, study vulgaris vitiligo MHC region in the Han population a SNPrs9468925 single nucleotide polymorphism with vitiligo phenotype provide important genetic basis for further study of the pathogenesis of vitiligo. Methods 5,566 patients with vitiligo and 6,462 cases of normal control MHC region single nucleotide polymorphism rs9468925 locus genotyping (AA, AG, GG) data are derived from our group vitiligo genome-wide association analysis of Illumina 610 chip, type data, after appropriate transformation of the data after the application of social science statistical package SPSS10.0 statistical analysis of the data. 1 case group and the control group genotype overall distribution differences statistically significant (χ 2 = 138.4, df = 2, P = of 8.85 x -31 ) allele distribution differences of the case group and the control group also has a significant (χ 2 = 136.49, df = 1, P = 1.56 × 10 -31 , OR = 0.73,95% CI :0.69-0 .77). Onset patients age ≤ 20 years of age compared with the control, rs9468925 locus genotype and allele distribution of the differences were statistically significant (the χ 2 = 140.93, df = 2, P = 2.50 × 10 -31 ; χ 2 = 140.42, df = 1, P = 2.16 × 10 -32 , OR = 0.68,95% CI: 0.63 -0.72). The incidence of patient age gt; 20-year-old with comparisons rs9468925 genotype and allele distribution difference was statistically significant (χ 2 = 43.87, df = 2, P = 2.97 × 10 < sup> -10 ; χ 2 = 43.23, df = 1, P = 4.87 × 10 -11 , OR 0.80,95% CI 0.74-0.85) . The incidence of patients ≤ 20 years of age and the incidence of patients gt; rs9468925 locus genotype and allele distribution between the ages of 20 differences were statistically significant (the χ 2 = 16.53, df = 2, P = 2.57 × 10 -4 ; χ 2 = 16.1, df = 1, P = 6.01 × 10 -5 , OR = 0.80,95% CI 0.74 - 0.85). Involved in lesion area lt; 5% of patients in the control comparison, the rs9468925 locus genotype and allele distribution of the differences were statistically significant (the χ 2 = 109.4, df = 2, P = 1.72 × 10 -24 ; χ 2 = 109.67, df = 1, P = 1.16 × 10 -25 , OR = 0.73,95 % CI :0.69-0 .77). The involved lesions ≥ 5% of patients and comparisons, rs9468925 locus genotype and allele distribution of the differences were statistically significant (the χ 2 = 63.79, df = 2, P = 1.41 × 10 -14 ; χ 2 = 58.71, df = 1, P = 1.83 × 10 -14 , OR = 0.72,95% CI: 0.66-0.78). Involving lesion area lt; ≥ 5% of patients in the 5% of the patients involved in lesion area between the rs9468925 locus genotype was statistically significant (χ 2 = 7.39, df = 2, P = 0.025) allele distribution difference was not statistically significant (χ 2 = 0.3, df = 1, P = 0.58, OR = 1.03, 95% CI :0.94-1 .12). 4 family history positive patients compared with the control, rs9468925 locus genotype and allele distribution of the differences were statistically significant (the χ 2 = 34.97, df = 2, P = 2.55 × 10 -8 ; χ 2 = 32.92, df = 1, P = 9.59 × 10 -9 , OR = 0.70,95% CI :0.63-0 .79 ). Family history negative patients compared with the control, rs9468925 locus genotype and allele distribution differences with statistical significance (χ 2 = 63.79, df = 2, P = 1.41 × 10 - 14 ; χ 2 = 58.71, df = 1, P = 1.83 × 10 -14 , OR = 0.72,95% CI :0.66-0 .78). Family history of patients with positive and negative patients between rs9468925 genotype and allele differences were not statistically significant (the χ 2 = 3.28, df = 2, P = 0.19; χ to 2 = 0.38, df = 1, P = 0.54, OR = 0.96,95% CI :0.85-1 .09). Associated with autoimmune disease patients and controls compare the rs9468925 locus genotype and allele distribution differences were statistically significant (the χ 2 = 14.23, df = 2, P = 0.001; χ 2 = 13.94, df = 1, P = 1.88 × 10 -4 , OR = 0.72,95% CI :0.60-0 .85). Not associated with autoimmune disease patients with comparisons rs9468925 genotype and allele distribution difference was statistically significant (χ 2 = 132.93, df = 2, P = 1.36 × 10 -29 ; χ 2 = 131.18, df = 1, P = 1.93 × 10 -30 , OR = 0.73,95% CI: 0.69 -0.77). Concomitant the rs9468925 locus genotype and allele distribution between patients with autoimmune diseases and is not associated with the autoimmune disease patients, there was no statistically significant difference in (the χ 2 = 0.43, df = 2 , P = 0.81; χ 2 = 0.57, df = 1, P = 0.45, OR = 1.09,95% CI :0.87-1 .37). 6. Localized patients compared with the control, rs9468925 locus genotype and allele distribution of the differences were statistically significant (the χ 2 = 38.04, df = 2, P = 5.48 × 10 -9 ; χ 2 = 37.06, df = 1, P = 1.14 × 10 -9 , OR = 0.79,95% CI :0.73-0 .85) . Sporadic patients compared with the control rs9468925 locus genotype and allele distribution differences with statistical significance (χ 2 = $ 12,183, df = 2, P = 3.51 × 10 -27 ; χ 2 = 119.87, df = 1, P = 6.76 × 10 -28 , OR = 0.70,95% CI :0.66-0 .75). Pan the hairstyle patients with comparisons rs9468925 genotype and allele distribution difference was statistically significant (χ 2 = 14.41, df = 2, P = 0.001; χ to 2 < / sup> = 13.31, df = 1, P = 2.64 × 10 -4 , OR = 0.79,95% CI :0.73-0 .85). Surface limb patients and controls compare the rs9468925 locus genotype and allele distribution differences statistically significance (χ the 2 = 17.00, df = 2, P = 2.04 × 10 - 4 ; χ 2 = 16.05, df = 1, P = 6.17 × 10 -5 , OR = 0.72,95% CI :0.62-0 .85). Clinical types of patients rs9468925 genotype distribution of the difference was statistically significant (the χ 2 = 13.98, df = 6, P = 0.03), allele distribution difference was statistically significant (χ 2 = 6.74, df = 3, P = 0.08). Conclusion 1.MHC area rs9468925 genetic polymorphism and Han unusual vitiligo susceptibility. Han Chinese patients with vitiligo MHC region rs9468925 genetic polymorphism and age of onset was a significant correlation. Han vitiligo patients MHC region rs9468925 genetic polymorphism with incidence area significantly. 4.MHC area rs9468925 genetic polymorphism and Han vitiligo clinical onset of type significant correlation. Rs9468925 genetic polymorphism of the MHC region are the presence or absence of a family history of vitiligo, whether associated with a weak effect of autoimmune disease, may be associated with vitiligo has a different genetic basis and pathogenesis-related.

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CLC: > Medicine, health > Dermatology and Venereology > Dermatology > Metabolic disorders of the skin > Vitiligo ( vitiligo )
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