The Association Analysis Of Genes Polymorphisms With Susceptibility To Systemic Sclerosis In Chinese Han Population

Backgroud:Systemic sclerosis (or systemic scleroderma, SSc) is a connective tissue disease characterized by tissue fibrosis, vascular endothelial injury and activation of the immune system. Its clinical spectrum varied from skin sclerosis to lethal damage to internal organs such as pulmonary hypertension, pulmonary fibrosis, kidney crisis. The etiology and pathogenesis is uncertain but studies have shown that genetic factors played an important role. International investigators have studied more than50single nucleotide polymorphisms (SNPs) of candidate genes, but the results are controversial. In the year2011, Europe and the United States published datas of two large-scale genome-wide association study(GWAS), and found some new loci of susceptibility in the SSc patients.Purpose:To verify the association of candidate genes and its single nucleotide polymorphisms from previous and GWAS studies to systemic sclerosis in Chinese Han populationMethods:A case-control study was applied in this study.A total of248systemic sclerosis patients, which are from the out patient department of dermatology and rheumatology in the Peking Union Medical College Hospital (PUMCH), and252controls which are from the physical examination center of the PUMCH were enrolled in this study. The genome DNA was extracted from peripheral blood of each subject. The method ofMassarray (designed by Sequenome) SNP analysis is adopted to detect50SNP loci in8candidate genes. Statistical analysis of both genotype and allele frequencies are done to detect the affection of genes to the susceptibility of SSc.Results:At last39SNP loci in8candidate genes were successfully detected. Three SNP sites were detected to have significant differences in alleles between the disease group and the control group.In detail, rs1062292inRHOB, OR=0.618(95%C10.400-0.956, p=0.030), rs2736340inFAM167A-BLK, OR=0.722(95%CI0.539-0.967, P=0.029), rs13277113inFAM167A-BLK, OR=1.335(95%CI1.013～1.760, P=0.040) have been found. There were no significant differences between the disease group and the control groupin the rest of SNP loci. There were no significant differences been found in genotypes between the disease group and the control group. Conclusion:RHOB and FAM167A-BLK are probably the susceptibility genes to SSc in Chinese Han population; SSc have high level of genetic heterogeneity. Genes which are confidently identified as the susceptible genes of SSc in other population, such as IL12RB2, TNIP1, PSOBS1C1, TBX21, TNFSF4, FAS, may not be the susceptible genes of SSc in Chinese Han population.