Objectives To systematically review evidence regarding the relationship between circulating interleukin-17 (IL-17) levels and rheumatoid arthritis (RA), and associations between polymorphisms in IL-17 genes and RA susceptibility. Method We performed a meta-analysis of serum/ plasma IL-17 levels in patients with RA and controls, and evaluated evidence of associations between the rs2275913, rs3819024, rs4711998 and rs8193036 polymorphisms in IL-17A and the rs763780 and rs2397084 polymorphisms in IL-17F and risk for RA. Results Fourteen studies including 3118 patients with RA and 2725 controls were included. Our meta-analysis revealed that IL-17 levels were significantly higher in the RA group than in the control group (p=3.1×10-6). Subgroup analysis using sample size showed increased IL-17 levels in samples from both small (n≤100) and large (n>100) RA groups (p=1.1×10-4 and p=0.008, respectively). We found evidence of associations between RA and alleles from the IL-17A rs2275913 and IL-17F rs763780 polymorphisms in Caucasians (p=0.003 and p=0.037, respectively). In addition, we found an association between RA and alleles of the IL-17A rs3819024 polymorphism in the pooled RA cohort compared with matched controls (p=0.033). However, no evidence of association was found between the IL-17F rs2397084, IL-17A rs4711998 and IL-17A rs8193036 polymorphisms and RA susceptibility. Conclusions Our meta-analysis revealed significantly higher circulating IL-17 levels in patients with RA, and found evidence of associations between the IL-17A rs2275913, IL-17F rs763780 and IL-17A rs3819024 polymorphisms and pathogenesis of RA.
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