Preliminary Results Of SNP Research In Chinese Scleroderma Patients

Backgroud:Systemic sclerosis (SSc or scleroderma) 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 and kidney crisis. The etiology and pathogenesis is unknown but studies have shown that genetic factors played an important role. International investigators have studied more than50single nucleotide polymorphisms (SNPs) of candidate genes, but many of them were only conflicting results. After2009, the Europe, the United States and South Korea have published sevearl studies of large-scale genome-wide association scan. In addition to further verifying the previously found susceptible loci associated with the disease, they also found some new.Purpose:To verify the association of candidate genes and its SNPs from previous studies and GWAS data to SSc in Chinese population, and do in-depth analysis of relationship between these SNPs and different phenotypes of SSc.Methods:In this study, Sequenom Massarray SNP analysis platform was adopted to detect32SNPs of different gene loci in265systemic sclerosis patients and122controls. Statistical analysis of both genotype and allele frequencies was done combined with subtype analysis of the clinical manifestations and serum antibodies spectrum.Results:MHC area’s rs7763822and rs7764491((p=0.004and0.0006respectively) and STAT4rs7574865(p=0.027) are associated with SSc; MHC rs3128930, rs7763822and rs7764491are associated with anti-Scl-70autoantibodies(p values as0.001,0.00001and0.00001respectively); BANK1rs17266594and STAT4rs7574865are related to ACA autoantibodies (p=0.04and p=0.04); EXOC-IRF4rs12206548and rs2493040are related tosubtyping (p=0.006and p=0.007)Conclusion:STAT4is a susceptibility gene to SSc in Chinese population; MHC genes are in the strongest association with SSc in Chinese population; multiple gene loci are associated with SSc subtype, anti-Scl-70antibodies and ACA antibodies.