title: Association of a polymorphism of the interleukin 6 receptor gene with chronic kidney disease in Japanese individuals.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  The rs4845625 of IL6R may be a susceptibility locus for CKD in Japanese individuals.
authors.affiliation: Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Horibe
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Fujimaki
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Oguri
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Kato
authors.forename: Reiko
authors.initials: R
authors.lastname: Matsuoka
authors.forename: Shintaro
authors.initials: S
authors.lastname: Abe
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Tokoro
authors.forename: Masazumi
authors.initials: M
authors.lastname: Arai
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Noda
authors.forename: Sachiro
authors.initials: S
authors.lastname: Watanabe
authors.forename: Yoshiji
authors.initials: Y
authors.lastname: Yamada
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005919:Glomerular Filtration Rate / Q000235:genetics; D006801:Humans; D007564:Japan / Q000453:epidemiology; D007668:Kidney / Q000503:physiopathology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D019947:Receptors, Interleukin-6 / Q000235:genetics*; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D012307:Risk Factors
chemical_list: C508603:IL6R protein, human; D019947:Receptors, Interleukin-6
keywords: genetics; interleukin-6; kidney failure; polymorphism; receptors; renal insufficiency