Association of candidate gene polymorphisms with chronic kidney disease in Japanese individuals with hypertension.

Although hypertension has been recognized as a risk factor for chronic kidney disease (CKD), the genetic factors for predisposition to CKD in individuals with hypertension remain largely unknown. The purpose of this study was to identify the genetic variants that confer susceptibility to CKD among individuals with hypertension. The study population comprised 3696 Japanese individuals with hypertension (2265 men, 1431 women), including 1257 individuals (789 men, 468 women) with CKD (estimated glomerular filtration rate (eGFR) <60 ml min(-1) per 1.73 m(2)) and 2439 controls (1476 men, 963 women; eGFR >or=60 ml min(-1) per 1.73 m(2)). The genotypes for 30 polymorphisms of 26 candidate genes were determined. An initial screening of allele frequencies by the chi(2)-test revealed that eight polymorphisms were significantly (false discovery rate <0.05) associated with the prevalence of CKD in hypertensive individuals. Subsequent multivariable logistic regression analysis with adjustment for covariates as well as a stepwise forward selection procedure revealed that the T --> C (Val591Ala) polymorphism of APOB (rs679899), the -681C --> G polymorphism of PPARG (rs10865710), the T --> C (Cys1367Arg) polymorphism of WRN (rs1346044), the -850C --> T polymorphism of TNF (rs1799724), the -219G --> T polymorphism of APOE (rs405509), the C --> T polymorphism of PTGS1 (rs883484) and the 41A --> G (Glu14Gly) polymorphism of ACAT2 (rs9658625) were significantly (P<0.05) associated with the prevalence of CKD. Our results suggest that APOB, WRN, ACAT2, APOE, PPARG, TNF and PTGS1 are susceptibility loci for CKD among Japanese individuals with hypertension. Determination of the genotypes for these polymorphisms may prove informative for the assessment of genetic risk for CKD among such individuals.