Polymorphisms in the 5’-UTR region of IL-10RA gene are associated with chronic kidney disease

Abstract

Chronic kidney disease (CKD), characterized by the progressive, irreversible loss of kidney function, has been a significant socioeconomic burden. Thus, identifying potential treatment targets and incipient biological risk indicators for CKD prediction is crucial. Recently several studies revealed that IL-10, IL-10RA, and IL-10RB genes were involved in the development of vascular complications in hypertension and stroke. The purpose of this study was to evaluate the association between CKD and IL-10, IL-10RA, and IL-10RB gene polymorphisms in the Korean population. Ninety-two CKD patients and 312 control subjects participated in the study. Blood samples were drawn for biochemical measurements and genetic polymorphism analysis. To analyze the genotypes of each single nucleotide polymorphism (SNP), PCR products were sequenced by a DNA analyzer. The four SNPs of the IL-10RA gene showed significant associations between CKD and the control group in the codominant1 (rs2228054, rs2228055, and rs9610, OR = 0.48, 95% CI = 0.28–0.82, p = 0.007; rs2256111, OR = 0.49, 95% CI = 0.29–0.83, p = 0.008, respectively), dominant (rs2228054, rs2228055, and rs9610, OR = 0.59, 95% CI = 0.36–0.95, p = 0.028; rs2256111, OR = 0.60, 95% CI = 0.38–0.97, p = 0.037, respectively), and over-dominant model (rs2228054 and rs2228055, OR = 0.47, 95% CI = 0.28–0.79, p = 0.0034; rs9610, OR = 0.48, 95% CI = 0.29–0.80, p = 0.0037; rs2256111, OR = 0.49, 95% CI = 0.29–0.80, p = 0.0039). The four SNPs of IL-10 showed significant associations with the estimated glomerular filtration rate (eGFR) and C-reactive protein (CRP), with the minor homozygote genotype of each SNP associated with lower eGFRs and decreased CRP levels ( p < 0.05, p = 0.001, respectively). The two SNPs of IL-10RA showed significant associations with the CRP levels ( p < 0.05). The two SNPs of IL-10RB were significantly associated with the eGFR, with the minor homozygote genotype of each SNP associated with lower eGFRs ( p < 0.01). Our results show that IL-10RA gene variants are associated with CKD development. Additionally, this study suggests that SNPs of IL-10RA were associated with CRP levels in CKD.