Associations between circulating IL-17 levels and rheumatoid arthritis and between IL-17 gene polymorphisms and disease susceptibility: a meta-analysis.

Abstract

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. 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 <i>IL-17A</i> and the rs763780 and rs2397084 polymorphisms in <i>IL-17F</i> and risk for RA. 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 <i>IL-17A</i> rs2275913 and <i>IL-17F</i> rs763780 polymorphisms in Caucasians (p=0.003 and p=0.037, respectively). In addition, we found an association between RA and alleles of the <i>IL-17A</i> rs3819024 polymorphism in the pooled RA cohort compared with matched controls (p=0.033). However, no evidence of association was found between the <i>IL-17F</i> rs2397084, <i>IL-17A</i> rs4711998 and <i>IL-17A</i> rs8193036 polymorphisms and RA susceptibility. Our meta-analysis revealed significantly higher circulating IL-17 levels in patients with RA, and found evidence of associations between the <i>IL-17A</i> rs2275913, <i>IL-17F</i> rs763780 and <i>IL-17A</i> rs3819024 polymorphisms and pathogenesis of RA.