The purpose of the present study was to identify genetic variants that confer susceptibility to chronic kidney disease (CKD) in Japanese individuals with metabolic syndrome. The study population comprised 2150 Japanese individuals with metabolic syndrome, including 411 subjects with CKD [estimated glomerular filtration rate (eGFR) <50 mL/min/1.73m(2)] and 1739 controls (eGFR >/=60 mL/min/1.73m(2)). The genotypes for 100 polymorphisms of 80 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 nine polymorphisms of APOE, ABCA1, PTGS1, TNF, CPB2, AGTR1, OR13G1, and GNB3 were associated (P<0.05) with the prevalence of CKD. Among these polymorphisms, the -219G-->T polymorphism of APOE (rs405509) was most significantly associated with CKD in Japanese individuals with metabolic syndrome.