Polymorphisms in STAT 4 and IRF 5 increase the risk of systemic sclerosis: a meta‐analysis

Background Systemic sclerosis ( SS c) is the most severe connective tissue disorder. Recent studies have demonstrated that genetic factors may play a role in the development of SS c. The aim of this study was to investigate the association of signal transducer and activator of transcription 4 ( STAT 4) rs7574865 and interferon regulatory factor 5 ( IRF 5) rs2004640 polymorphisms with risk of SS c. Methods Case–control studies were obtained from the electronic database of P ub M ed, M edline, E mbase, and CNKI ( C hina N ational K nowledge I nfrastructure) up to D ecember 2013. The association between STAT 4 and IRF 5 polymorphisms and SS c susceptibility was assessed by pooled odds ratios ( OR s) and 95% confidence intervals ( CI ). Results Six related studies, including 4746 SS c cases and 7399 healthy controls, were pooled in this meta‐analysis. For STAT 4 polymorphism, we observed a statistically significant positive association between risk factor T allele carriers and SS c susceptibility ( OR = 1.37, 95% CI = 1.27–1.48, P < 0.00001) in the overall population. The presence of limited cutaneous (lc SS c) and diffuse cutaneous (dc SS c) scleroderma also showed a significant association with each of the genetic models ( P < 0.00001). For IRF 5 polymorphism, the T allele was shown to be strongly associated with increased SS c risk ( OR = 1.27, 95% CI = 1.17–1.39, P < 0.00001). No significant heterogeneity between studies was found. Conclusions The results demonstrated that STAT 4 rs7574865 and IRF 5 rs2004640 G / T substitution are associated with a susceptibility to SS c, and they may serve as the SS c genetic susceptibility factor. These data confirmed that genetic polymorphisms may play a role in the development of SS c and have provided new insight into the pathogenesis of SS c.