Gene polymorphisms of interleukin-17 and interleukin-17 receptor are associated with end-stage kidney disease

Background: Inflammation could be a causal factor in progression of chronic kidney disease. To date, there is convincing experimental and clinical evidence to support the notion that interleukin (IL)-17-producing T cells contribute to kidney injury in renal diseases. However, the genetic relationship between end-stage renal disease (ESRD) and the T-helper 17 pathway has never been studied. In this study, we hypothesized that polymorphisms of IL-17 or their receptors may be associated with ESRD.

Methods: A total of 290 nondiabetic ESRD patients and 289 normal controls were included. We analyzed 13 single nucleotide polymorphisms located within the four genes of IL17A, IL17E, IL17RA and IL17RB.

Results: The ESRD patients had a significantly higher allele frequency compared to control subjects for the IL17E rs10137082*C and IL17RA rs4819554*A alleles. Genotyping analysis demonstrated that 2 SNPs among 13 were significantly associated with ESRD after adjusting for age and sex, which were shown by IL17E rs10137082 (odds ratio (OR) 1.48 in codominant 1, OR 1.54 in dominant, OR 1.47 in log-additive) and IL17RA rs4819554 (OR 1.46 in codominant 1, OR 1.79 in codominant 2, OR 1.54 in dominant, OR 1.39 in log-additive).

Conclusions: Two polymorphisms within the IL17E and IL17RA genes are associated with ESRD independent of age and sex. This is the first finding to suggest that genetic variations of IL17 genes affect the risk of development of ESRD.