Importance of STAT3 Polymorphisms on the Risk and Clinical Characteristics of Rheumatoid Arthritis

Abstract

Signal transducer and activator of transcription 3 (STAT3) has been introduced as one of the critical genetic factors in the pathogenesis of rheumatoid arthritis (RA). Single nucleotide polymorphisms (SNPs) in microRNA binding sites, known as miRSNPs, are a class of common variants in the 3′ untranslated regions of genes targeted by miRNAs. miRSNPs unbalance gene expression by disrupting the binding regions of microRNAs. In this study, we intended to evaluate the association of two miRSNPs with the risk of RA development and its clinical features. We studied 120 Iranian patients with RA and 125 non-RA subjects as controls. The genotypes and alleles of rs1053005 and rs1053023 in each individual were assessed by the high-resolution melting method. The distribution of STAT3 variants did not differ markedly in RA patients compared to healthy controls. Stratification analysis revealed that rs1053005 was linked with a higher concentration of C-reactive protein and an increased erythrocyte sedimentation rate, two indicators of inflammation and disease activity in RA patients. The rs1053023 variant was correlated with higher levels of creatinine as an indicator of renal involvement. Our data demonstrate an association between STAT3 variants and clinical characteristics of RA, such as disease activity and probably kidney impairment.  However, we did not observe a significant relationship between the two targeted variants and a predisposition to RA.