Interleukin-10-1082A/G polymorphism is associated with renal parenchymal damage in congenital anomalies of the kidney and urinary tract

Nephrology (Carlton). 2019 Feb;24(2):213-220. doi: 10.1111/nep.13229.

Abstract

Aim: The aim of the study was to investigate whether the functional IL10-1082A/G polymorphism exert a role in congenital anomalies of the kidney and urinary tract (CAKUT) in children. Also, the serum IL-10 and its association with genotype and renal parenchymal damage in CAKUT were explored.

Methods: In the current case-control study, 134 paediatric cases of CAKUT and 382 unrelated controls were included. The genotyping of IL10-1082A/G polymorphism was performed by amplification refractory mutation system-PCR and IL-10 serum level was determined by ELISA.

Results: Although, the genotype and allelic frequencies of IL10-1082 A/G polymorphism in cases and controls were similar (χ2 = 0.459; P = 0.79 and χ2 = 0.426; P = 0.51, respectively), significant different genotype distribution between patients with or without parenchymal damage/reduction was observed (χ2 = 6.9; P = 0.032). The GG-genotype was more frequent in cases with renal parenchymal damage/reduction compared to patients with preserved parenchyma (22% vs. 9%; OR = 2.987; 95% CI = 0.979-9.468; P = 0.031). On the contrary, the heterozygous genotype was less frequent among cases with parenchymal damage/reduction compared to cases with preserved parenchyma (39% vs. 59%; OR = 0.453; 95% CI = 0.214-0.958; P = 0.024). Additionally, the serum IL-10 was significantly higher in CAKUT patients compared to age-sex-matched controls (median 11.98; IQR: 7.14-31.6 vs. 5.92; IQR: 4.68-14.8; P = 0.0057). Among carriers of GG-genotype significantly higher IL-10 level was detected in cases with parenchymal damage/reduction, than cases with preserved parenchyma (P = 0.028).

Conclusion: Our results suggested that the functional -1082A/G polymorphism in IL10 is associated with risk of renal parenchymal damage/reduction rather than genetic predisposition to CAKUT. Additionally, our study supposes that immunoregulatory cytokine IL-10 might have a significant role in CAKUT.

Keywords: Interleukin-10; cytokine; genotype; renal parenchymal damage/reduction.; rs1800896.

MeSH terms

  • Adolescent
  • Biopsy
  • Case-Control Studies
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Infant
  • Interleukin-10 / blood
  • Interleukin-10 / genetics*
  • Kidney / pathology*
  • Male
  • Parenchymal Tissue / pathology*
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Risk Factors
  • Urogenital Abnormalities / blood
  • Urogenital Abnormalities / genetics*
  • Urogenital Abnormalities / pathology*
  • Vesico-Ureteral Reflux / blood
  • Vesico-Ureteral Reflux / genetics*
  • Vesico-Ureteral Reflux / pathology*

Substances

  • IL10 protein, human
  • Interleukin-10

Supplementary concepts

  • Cakut