The autoimmune regulator (AIRE) gene controls autoimmunity via its transcript AIRE protein that suppresses naïve T cells during central selection. The role of AIRE polymorphism in rheumatoid arthritis (RA) autoimmunity remains elusive. This study aimed to investigate the association of two selected SNPs, namely, rs760426 and rs2075876, with RA susceptibility in the Suez Canal Zone population. The study population included 100 RA patients, and the control group included 100 healthy subjects who were age- and sex-matched to the RA group. SNP genotyping was performed using real-time polymerase chain reaction-based allelic discrimination assay, the odds ratio was defined to assess the strength of the association. For rs760426, combining genotypes data revealed a significant increase for A/G genotype in the RA cases (47%, n = 47) than in the control group (27%, n = 27) in both co-dominant and over-dominant models (P = 0.013 and 0.003 respectively). In addition, rs760426 correlated to duration of RA (P = 0.031) and anti-cyclic citrullinated peptide antibody (P = 0.021). For rs2075876, there was a significant increase in the A/A genotype in RA patients compared with control subjects. In the co-dominant model, the frequency of A/A was 14% and 7% respectively (P = 0.02). In contrast to rs760426, rs2075876 associated with the risk of increased body mass index (P = 0.014) and the positivity of rheumatoid factor (RF) (P = 0.043). The frequency of minor alleles, G allele in rs760426 SNP, and A allele in rs2075876 was higher in RA patients than in control. The haplotype frequency of both G and A alleles in rs760426 and rs2075876 receptively was 11% in RA group with statistically significant difference (P = <0.001) between RA patients and healthy control. SNPs rs760426 and rs2075876 in the AIRE gene may contribute to the risk for RA susceptibility. These two polymorphisms were associated with variable risk factors and predictive biomarkers for RA. The mutant allele (G) of rs760426 SNP has significant indication of poor prognosis.
Keywords: AIRE; Gene; Haplotype; Polymorphism.