Several studies have reported genetic polymorphisms at the IL-23/IL-17 axis linked to rheumatoid arthritis (RA) in many populations. We aimed to investigate the association of IL-17A rs2275913 and IL-23R rs11209026 polymorphisms with susceptibility to RA and, disease clinical features and the serum level of IL-17A in Egyptian patients. This case-control study included 94 RA cases and 74 controls. TaqMan genotyping assays were used for detection of gene polymorphism and the enzyme-linked immunosorbent assay was used to quantify IL-17A serum level. There was significant difference between RA patients and controls in genotypic distribution and allelic frequency of IL-17A rs 2275913 (p < 0.0001). The GG genotype had 7 times higher risk for RA development (OR=7.04: 95% CI 2.11:23.46, p value= 0.001). Also, GG genotype was associated with higher level of serum IL-17 A compared to GA and AA genotypes (p < 0.0001). Moreover, patients carrying the GG genotype had higher disease activity score 28 (DAS28) score (4.99±0.84) compared to patients with GA (2.73±0.52, p < 0.0001) and patients with AA genotypes (2.67±0.41, p < 0.0001). Genotypic distribution of IL-23R rs11209026 was significantly different between RA patients and controls (p < 0.0001), but there was no difference between the allelic frequency in both groups (p=0.08). IL-23R rs11209026 SNP was not a risk for RA development. However, DAS28 was lower in AA genotype than AG and GG genotypes (p=0.002, p=0.009 respectively). The mean serum IL-17A level was higher among the RA patients (39.07±10.47 pg./ mL) compared to controls (15.23±1.88 pg/ mL; p < 0.0001). Also, there was a positive correlation between IL-17A serum level and DAS28 score (Spearman r = 0.42; p value < 0.0001). We concluded that the variant IL-17A (rs2275913) genotype could be a risk factor for RA in our population and IL-17A may play a crucial role in the development and pathogenesis of RA.

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