CTLA-4+49 Polymorphism and Susceptibility to Rheumatoid Arthritis in Pakistani Population

Cytotoxic T lymphocyte Antigen 4 (CTLA-4), similar to co-stimulatory molecule CD28, plays an important role in down regulation of T cell activation..CLTA-4 binds to B7 with much greater affinity as compared to CD28, thus limiting the enhanced activation of T cells and preventing autoimmune diseases. CTLA-4 gene has an important variation rs231775 which interferes with the functioning of CTLA-4 causing uncontrolled activation of T cells. rs231775 may prone individuals to development of rheumatoid arthritis (RA), a severe autoimmune disease. This study aims to find the possible role of rs231775 polymorphism and the risk factors smoking, hypertension and diabetes in conferring susceptibility to RA in Pakistani population. Allele specific PCR based strategy was used to amplify rs231775 in samples of 100 RA patients and 100 age and sex matched healthy individuals. GG genotype of rs231775 polymorphism was found to increase the risk of RA development by 3.0186 times (OR 3.0186; 95% CI 1.6774-5.4322). Smoking increased the risk of RA development by 3.1672 times (OR or 3.1672; 95% CI 1.77665.6462). Diabetes was found to increase the risk of RA development by 2.172 times (OR 2.172; 95% CI 1.18973.9669). Hypertension also increased the risk of RA development by 2.280 times (OR 2.280; 95% CI 1.2676-4.1021). It can be concluded that smoking, diabetes, hypertension and rs231775 play an important role in development of RA in Pakistani population.