The purpose of the present study was to identify genetic variants which confer susceptibility to chronic kidney disease (CKD) in high- or low-risk subjects defined by conventional risk factors separately. The study population comprised 2828 Japanese individuals, including 434 subjects with CKD [estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2] and 2394 controls (eGFR ≥60 ml/min/ 1.73 m2). The 1012 high-risk subjects had both hypertension and diabetes mellitus, and the 1816 low-risk subjects had none of these conditions. The genotypes for 296 polymorphisms of 202 candidate genes were determined. The Chi-square test, multivariable logistic regression analysis with adjustment for covariates, as well as a stepwise forward selection procedure revealed that ten different polymorphisms were associated (P<0.05) with the prevalence of CKD in high- or low-risk subjects: the -519A↷G polymorphism of MMP1, the 1061A↷G (Ile405Val) polymorphism of CETP, the A↷G (Lys45Glu) polymorphism of MMP3, the -219G↷T polymorphism of APOE, the A↷G (Ile1205Val) polymorphism of COL3A1, the -863C↷A polymorphism of TNF, and the 1454C↷G (Leu125Val) polymorphism of PECAM1 in high-risk subjects; and the 1167C↷T (Asn389Asn) polymorphism of TGFBR2, the 2386A↷G (Ile796Val) polymorphism of SCAP, and the TAAA↷del polymorphism of PDE4D in low-risk subjects. Among these polymorphisms, the -519A↷G polymorphism of MMP1 and the 1167C↷T (Asn389Asn) polymorphism of TGFBR2 were most significantly associated with CKD in high- or low-risk individuals, respectively. These results suggest that polymorphisms associated with CKD may differ among high- or low-risk subjects. Stratification of subjects according to conventional risk factors may thus be important for personalized prevention of CKD based on genetic information.

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