Association of a polymorphism of the interleukin 6 receptor gene with chronic kidney disease in Japanese individuals

Nephrology (Carlton). 2015 Apr;20(4):273-8. doi: 10.1111/nep.12381.

Abstract

Aim: Various loci and genes that confer susceptibility to coronary artery disease (CAD) have been identified in Caucasian populations by genome-wide association studies (GWASs). The aim of the present study was to examine a possible association of chronic kidney disease (CKD) with 29 polymorphisms previously identified as susceptibility loci for CAD by meta-analyses of GWASs.

Methods: The study population comprised 2247 Japanese individuals, including 1588 subjects with CKD [estimated glomerular filtration rate (eGFR) of <60 mL min(-1) 1.73 m(-2) ] and 659 controls (eGFR of ≥90 mL min(-1) 1.73 m(-2) ). The genotypes for 29 polymorphisms of 28 candidate genes were determined.

Results: The χ(2) test revealed that rs4845625 (T→C) of IL6R, rs4773144 (A→G) of COL4A1, rs9319428 (G→A) of FLT1, and rs46522 (T→C) of UBE2Z were significantly (P < 0.05) related to CKD. Multivariable logistic regression analysis with adjustment for age, sex, body mass index, and the prevalence of smoking, hypertension, diabetes mellitus, and dyslipidaemia revealed that rs4845625 of IL6R (P = 0.0008; dominant model; odds ratio, 1.49), rs4773144 of COL4A1 (P = 0.0252; dominant model; odds ratio, 1.28), and rs9319428 of FLT1 (P = 0.0260: additive model; odds ratio, 0.77) were significantly associated with CKD. The serum concentration of creatinine was significantly (P = 0.0065) greater and eGFR was significantly (P = 0.0009) lower in individuals with the TC or CC genotype of IL6R than in those with the TT genotype.

Conclusion: The rs4845625 of IL6R may be a susceptibility locus for CKD in Japanese individuals.

Keywords: genetics; interleukin-6; kidney failure; polymorphism; receptors; renal insufficiency.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Asian People / genetics*
  • Case-Control Studies
  • Chi-Square Distribution
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Glomerular Filtration Rate / genetics
  • Humans
  • Japan / epidemiology
  • Kidney / physiopathology
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Odds Ratio
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Receptors, Interleukin-6 / genetics*
  • Renal Insufficiency, Chronic / diagnosis
  • Renal Insufficiency, Chronic / ethnology
  • Renal Insufficiency, Chronic / genetics*
  • Renal Insufficiency, Chronic / physiopathology
  • Risk Factors

Substances

  • IL6R protein, human
  • Receptors, Interleukin-6