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Single Nucleotide Polymorphism rs2075876 in AIRE Gene is a Strong Rheumatoid Arthritis Determinant

Rheumatoid arthritis (RA) is a progressive and common autoimmune disease with multifactorial etiology. Several pieces of research show that genetic factors play a major role in the incidence of RA. Several genome-wide association studies (GWAS) have identified the autoimmune regulator (AIRE) gene as one of the candidate loci. This gene encodes a transcription factor, which is involved in the presentation of self-antigens and the negative selection of self-reactive T-cells in the thymus. Studies have indicated that single nucleotide polymorphisms (SNPs) in the AIRE gene can change the gene expression and/or function. In the present study, we assessed the possible association between SNP rs2075876 (intronic variant) in the AIRE gene with RA risk in the Iranian population. A case-control study using 56 RA patients and 58 control subjects was undertaken to evaluate rs2075876 genotypes using the real-time PCR high resolution melting method (HRM). Logistic regression analysis demonstrates that homozygous AA and heterozygous AG genotypes compared with GG genotype increase the risk of RA (AA vs. GG; OR=16.43; 95% CI [5.33-50.71] and AG vs. GG; OR=3.21; 95% CI [1.22-8.45]). Also, individuals with allele A were more frequently affected with RA than subjects with G allele (OR=5.81; 95% CI [3.28-10.30]). Furthermore, in the patient group, we found a significant correlation between erythrocyte sedimentation rate and C-reactive protein concentration with rs2075876 polymorphism (P<0.05). Our findings propose a substantial correlation between rs2075876 polymorphism and RA risk.