Rheumatoid Arthritis (RA) is an autoimmune disorder where multiple cytokines including IL-17A and IL-17F produced by T helper cell 17 (Th17), contribute to its pathogenesis. By initiating inflammatory responses in joints Th17 act as pathogenic driver leading to bone and cartilage destruction in RA patients. Hence, the planned study was aimed to estimate IL-17 gene polymorphism association with RA susceptibility in Pakistani population. The present study included 100 subjects (50 RA patients and 50 healthy controls). Blood samples were taken and DNA was isolated for genotyping purpose. Chi square and Logistic regression analysis was performed to check the association of selected SNPs with RA. For rs2397084 and rs763780 polymorphism T allele acted as significant risk factor as compared to the reference C allele. TT vs. CC comparison in rs2397084 showed that T allele is a risk factor (OR 5.538; 95%Cl 1.757-17.458) in RA susceptibility. In case of rs763780 heterozygous CT (OR 10.80; 95% Cl 3.736-31.218) and homozygous mutant TT (OR 7.50; 95% Cl 2.360-23.831) genotypes proved to be a potential risk for RA patients. The significant differences in allelic and genotypic frequencies were observed for both SNPs. While for rs2275913 significantly varied frequency was observed only for dominant model of inheritance and non significant differences were seen at allelic level. Variation at all these three polymorphic sites substituted mutant amino acids leading to further functional changes in protein structure. Three polymorphic sites rs2275913, rs763780 and rs2397084 positioned on IL-17 gene were significantly strong factors in RA incidence among Pakistani population as they alter normal function of inflammatory cytokine IL-17.
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