Association of CTLA-4 (+49A/G) polymorphism and susceptibility of developing rheumatoid arthritis in an Iraqi Arab population

Background: The gene responsible for encoding the protein of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) has been found to be associated with rheumatoid arthritis (RA) in different ethnic populations. But the association of +49A/G CTLA-4 polymorphism with susceptibility of RA among Iraqi Arab populations has not yet been determined. Methods: One hundred and seventy-eight patients were examined, 67 of them were males (mean age 54.71 +/- 10.4 years), while 167 were examined for the control group, of whom 64 were males and the rest were females. CTLA-4 DNA genotyping was carried on to determine the +49 A/G (rs231775) polymorphism using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Enzyme-linked immunosorbent assay (ELISA) was also applied here to measure the antibodies level for cyclic citrullinated peptides (antiCCP) and Rheumatoid factor (RF). Results: The frequency of AG and GG genotypes in CTLA-4 + 49 were significantly higher among RA patients in comparing with controls (55.61% vs 42.51%, OR = 2.18, 95% CI = 1.62-3.79, P = 0.003) and (20.22% vs 10.77%, OR = 2.61, 95% CI = 1.31-6.46, P = 0.002) respectively. G allele frequency was also significantly higher among RA cases (52.24% vs. 31.73%, OR = 3.02; 95% CI = 1.61-7.39, P = 0.001). The frequencies of the AA genotype and A allele, however, were significantly lower in cases than controls (24.15% vs 46.70%, P = 0.001) and (47.75% vs 68.26%, P = 0.001) respectively. Moreover, the levels of Anti-CCP and RF were raised significantly among RA patients than controls (P = 0.0001), but none of these parameters were correlated with genotypes of CTLA-4. Conclusions: Carries of CTLA-4 + 49 AG and GG alleles were at a high risk of developing functional disability of RA, unlike the AA allele carriers.