Influence of the IL17A and IL17F gene polymorphisms on the long-term kidney allograft function and return to dialysis after kidney transplantation

Clin Transplant. 2015 Dec;29(12):1187-94. doi: 10.1111/ctr.12649. Epub 2015 Nov 3.

Abstract

The immune response after allogenic transplantation is a complex phenomenon involving cytokines, chemokines, and other mediators of inflammation. The aim of this study was to evaluate the influence of the IL17A and IL17F gene polymorphisms on long-term kidney allograft function, graft function loss/return to dialysis, and mortality after kidney transplantation. This study enrolled 269 Caucasian deceased donor renal transplant recipients. The rs2275913:G>A (-197G>A) polymorphism within the IL17A gene promoter and rs2397084:T>C (Glu126Gly), rs11465553:G>A (Val155Ile), and rs763780:T>C (His167Arg) polymorphisms within the IL17F gene were genotyped. Creatinine concentrations 12, 24, 36, 48, and 60 months after transplantation were significantly higher in recipients with the rs2275913:A>G IL17A GG genotype (GG vs. GA + AA: p = 0.03, p = 0.004, p = 0.006, p = 0.03, p = 0.04, respectively). Moreover, the GG genotype was statistically significantly associated with increased risk of delayed graft function. This association remained significant in multivariate regression analysis adjusted for recipients' age and sex. In the case of the rs11465553, IL17F univariate Cox regression analysis showed statistically significant association of GA genotype with higher risk of graft loss/return to dialysis (GA vs. GG: HR = 2.795, 95%CI = 1.031-7.579, p = 0.04). The results of our study suggest that the GG genotype of the rs2275913 IL17A gene promoter polymorphism is associated with significantly impaired long-term kidney allograft function, whereas the GA genotype of the rs11465553 IL17F gene polymorphism may be associated with a significantly higher risk of graft function loss and return to dialysis after kidney transplantation.

Keywords: dialysis; function; graft; interleukin-17; kidney.

MeSH terms

  • Allografts
  • Female
  • Follow-Up Studies
  • Genotype
  • Glomerular Filtration Rate
  • Graft Rejection / genetics
  • Graft Survival / genetics*
  • Humans
  • Interleukin-17 / genetics*
  • Kidney Failure, Chronic / surgery
  • Kidney Function Tests
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Postoperative Complications*
  • Prognosis
  • Promoter Regions, Genetic / genetics
  • Renal Dialysis / mortality*
  • Risk Factors
  • Survival Rate

Substances

  • IL17A protein, human
  • IL17F protein, human
  • Interleukin-17