Genetic Analysis of IL-17 Gene Polymorphisms in Gout in a Male Chinese Han Population

Abstract

Interleukin (IL)-17 is a proinflammatory cytokine mainly secreted by activated T helper 17 cells and involved in inflammatory immune responses. This study aimed to investigate the association between IL-17 variants as well as serum IL-17 levels with gout in male Chinese Han individuals. A total of 1,101 male gout patients and 1,239 ethic-matched controls were enrolled. Genetic distributions of three variants (rs2275913 in IL-17A, rs763780 in IL-17F, and rs4819554 in IL-17RA) were detected by real-time polymerase chain reaction using the Taqman probe method. The plasma concentrations of IL-17A and IL-17F were measured in 228 gout patients and 198 controls that came from above samples by an enzyme-linked immunosorbent assay. No significant differences were observed in the genetic distribution of these polymorphisms between cases and controls (rs2275913: χ2 = 0.15, p = 0.928 by genotype, χ2 = 0.14, p = 0.711 by allele; rs763780: χ2 = 2.24, p = 0.326 by genotype, χ2 = 0.26, p = 0.609 by allele; rs4819554: χ2 = 1.79, p = 0.409 by genotype, χ2 = 1.46, p = 0.227 by allele). Levels of serum IL-17A and IL-17F were significantly decreased in gout patients (both p<0.001). However, no difference was observed in acute gout patients between different genotypic carriers of rs2275913 and rs763780 regarding serum IL-17A and IL-17F levels (p>0.05). Although the genetic variants in IL-17 we studied in this research do not appear to be involved in the development of gout in male Chinese Han individuals, the IL-17 cytokine family may participate in gouty inflammation in an undefined way, which requires further validation.

Fig 1. Levels of serum IL-17A and IL-17F in the AG, IG and control groups.

Serum IL-17A and IL-17F levels of 78 AG patients, 150 IG patients and 198 control subjects were detected using Elisa kit. Expression of serum IL-17A and IL-17F were significantly decreased in the AG and IG group compared with controls (P<0.001; respectively), whereas no significant difference was observed between the AG and IG groups (both P>0.05). AG represents acute gout; IG represents intercritical periods of gout. The ANOVA and Bonferroni's test methods were used. The statistical significance was set at P<0.05.

Fig 2. Association of the IL-17 polymorphisms with serum IL-17 levels in AG patients.

The serum IL-17A and IL-17F level were measured in different genotype carriers from AG patients. A) The expression of IL-17A level was no difference between the 15 AA homozygotes, 24 AG heterozygotes carriers and 9 GG homozygotes carriers of IL-17A rs2275913 polymorphism. (P>0.05; respectively); B) The expression of IL-17F level was no difference between the 2 CC homozygotes, 14 CT heterozygotes carriers and 62 TT homozygotes carriers of IL-17F rs763780 polymorphism (P>0.05; respectively).