Association of three functional polymorphisms in the NLRP3 gene with susceptibility to rheumatoid arthritis in Iranian population.

Rheumatoid arthritis (RA) is a complex systemic autoimmune disorder with multifactorial nature. Numerous previous studies have shown that several genes are involved in the pathogenesis and have increased the risk of RA. The Nod-like receptor pyrin domain containing 3 (NLRP3) involved in the regulation of innate immunity which its upregulation in RA have previously been reported.

To evaluate any correlation between 3 functional polymorphisms of NLRP3 and its gene expression and subsequently to RA risk.

One hundred and fourteen patients with RA and 120 healthy participants were recruited in this case-control study. Genotyping of rs4612666 (intronic variant), rs10754558 (3'UTR variant), and rs6672995 (downstream variant) were performed applying the real-time polymerase chain reaction high-resolution melting (HRM) method.

Based on logistic regression analysis, subjects with CC genotype and C allele in rs4612666 had increased the risk of RA (OR for CC genotype= 3.10; 95%CI [1.78-8.26]/ OR for C allele= 2.00; 95%CI [1.45-3.10]). Furthermore, in the patient groups, there was a significant relationship between the concentration of C-reactive protein (CRP) with rs4612666 and rs10754558 polymorphism (P< 0.05). Besides, our results revealed no important association between the genotype and allele frequency of rs10754558 and rs6672995 with the risk of RA (P> 0.05).

Our findings propose a considerable association between rs4612666 polymorphism and a rise of the risk of RA. Moreover, rs4612666 and rs10754558 were correlated with disease activity in the Iranian population.