Association of Polymorphisms in the NLRP3 Gene and Rheumatoid Arthritis in Iranian Patients

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 increased risk of RA. The Nod-like receptor pyrin domain containing 3 (NLRP3) is involved in the regulation of innate immunity and its upregulation has previously been reported in RA. Objective: To evaluate the correlation between 3 functional polymorphisms of NLRP3 and its gene expression and RA risk. Methods: One hundred and fourteen patients with RA and 120 healthy participants were recruited to this case-control study. Genotyping of rs4612666 (intronic variant), rs10754558 (3UTR variant), and rs6672995 (downstream variant) were performed applying the realtime polymerase chain reaction highresolution melting (HRM) method. Results: Based on logistic regression analysis, subjects with CC genotype and C allele in rs4612666 had increased 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) and rs4612666 and rs10754558 polymorphism (P<0.05). Besides, our results revealed no significant association between the genotype and allele frequency of rs10754558 and rs6672995 and the risk of RA (P>0.05). Conclusion: Our findings propose a significant association between rs4612666 polymorphism and increased risk of RA in the Iranian population. Moreover, rs4612666 and rs10754558 were correlated with disease activity.