Association of a Functional Single Nucleotide Polymorphism (rs874040) in the RBPJ Gene with Susceptibility to Rheumatoid Arthritis in Iranian Population

en Association of a Functional Single Nucleotide Polymorphism (rs874040) in the RBPJ Gene with Susceptibility to Rheumatoid Arthritis in Iranian Population Background: Rheumatoid Arthritis (RA) is a progressive, heterogeneous, and common multifactorial autoimmune disease. Several Genome-Wide Association Studies (GWASs) have revealed more than 100 risk loci for RA. One of these loci is a functional single nucleotide polymorphism (rs874040; G>C) near the recombination signal-binding protein for the immunoglobulin kappa J region (RBPJ) gene. RBPJ can convert into a transcriptional activator upon activation of the canonical Notch pathway. Notch signaling has recently emerged as an important regulator of immune responses in inflammation and autoimmune diseases. In the present study, the possible association between SNP rs874040 (G>C) upstream of the RBPJ gene with RA risk was assessed in Iranian population. Methods: A case-control study including 60 RA patients and 44 control subjects was conducted to estimate rs874040 genotypes using real‑time polymerase chain reaction High Resolution Melting (HRM) method. Results: Logistic regression analysis indicated that homozygous CC and heterozygous GC genotypes increase the risk of RA compared with GG genotype (CC vs. GG; OR=11.36; 95% CI [3.93-33.33] and CG vs. GG; OR=3.78; 95% CI [1.30-10. 98]). Besides, subjects with C allele were more frequently affected with RA than subjects with G allele (OR=10.42; 95% CI [5.21-20.83]). Furthermore, in the patient group, a significant correlation was found between C-reactive protein concentrations and rs874040 polymorphism (p<0.05). Conclusion: Our findings propose a substantial correlation between rs874040 polymorphism and RA risk in Iranian population. Genotype, Genome-Wide Association Study, Iran, Rheumatoid arthritis, Single nucleotide polymorphisms 166 170 https://www.ajmb.org/En/Article.aspx?id=40469 https://www.ajmb.org/PDF/En/FullText/40469.pdf MansourSalesiDepartment of Internal Medicine, Faculty of Medicine, Isfahan University of Medical Science, Isfahan, Iran61763Mahdieh OboodiyatDepartment of Internal Medicine, Faculty of Medicine, Isfahan University of Medical Science, Isfahan, Iran61764RasoulSalehiDepartment of Genetics and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran61765BahramPakzad61766