Association between the IL17RA rs4819554 polymorphism and reduced renal filtration rate in the Spanish RENASTUR cohort

Abstract

DNA variants at the genes that encode components of the IL17-pathway may contribute to the risk of impaired renal function/chronic kidney disease. Our aim was to determine whether common IL17RA single nucleotide polymorphisms (SNPs) were associated with a reduced estimated glomerular filtration rate (eGFR) in a cohort of healthy elderly individuals (n=650). We found a significantly higher frequency of SNP rs4819554 AA homozygotes among individuals with eGFR<60 ml/min/1.73 m(2) (n=90) (p=0.005, OR=2.11; 1.26-3.54), an effect that was independent of the presence of type 2 diabetes. Allele rs4819554 A had been associated to the risk of developing end stage renal disease, and was also linked to an increased expression of the IL17RA protein and higher levels of Th17 cell subsets. A scenario in which the pro-inflammatory role of the IL17-pathway contributes to kidney damage might explain the association between Il17RA polymorphisms and an impaired renal function.

Keywords: Gene polymorphism; Glomerular filtration; IL17 pathway genes; Renal function.