Impact of miRNA-binding site polymorphisms in STAT3 gene on occurrence and clinical characteristics of systemic lupus erythematosus.

Abstract

Signal transducer and activator of transcription 3 (STAT3) is a major regulator of immune response and chronic inflammatory conditions acting through regulation of B cells, T-helper 17 (Th17) cells, and IL-17 production. Previous studies have demonstrated that dysregulation of STAT3 is crucial for SLE pathogenesis and disease severity. It is believed that single nucleotide polymorphisms (SNPs) located at the 3'-UTR sequence of the target genes could dysregulate their expression by disrupting the binding site of miRNAs. In the present study, we assessed the possible association between rs1053005 and rs1053023 SNPs at miRNA binding sites in the STAT3 gene and the risk of SLE in the Iranian population for the first time. 112 SLE cases and 120 healthy controls were genotyped for rs1053005 (A>G) and rs1053023 (A>G) polymorphisms in STAT3 using real-time PCR high resolution melting method (HRM). Our results revealed substantial associations between GG genotype and G allele of rs1053023 with enhanced risk of SLE (OR for GG genotype= 3.13; 95%CI [1.61-6.1], OR for G allele = 2.22; 95%CI [1.51-3.25]). However, no important correlations have been found between rs1053005 polymorphism and SLE susceptibility in this population (p>0.05). Moreover, stratification analysis showed that these polymorphisms are correlated with parameters indicating disease activity and more severe course of the disease. These factors include some laboratory test results and clinical manifestations such as renal involvements. The current study suggests a significant association between STAT3 polymorphisms and augmented risk of SLE, clinical symptoms, disease activity, and severity.