Abstract
BACKGROUND AND OBJECTIVES: Although genetic linkage analyses and association studies have implicated several loci and candidate genes in predisposition to chronic kidney disease (CKD), the genes that underlie genetic susceptibility to this condition have remained uncharacterized. The purpose of the present study was to identify genetic variants that confer susceptibility to CKD in Japanese individuals. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The study population comprised 5217 Japanese individuals (2955 men, 2262 women), including 778 subjects (480 men, 298 women) with CKD [estimated GFR (eGFR), <50 ml min(-1) 1.73 m(-2)] and 4439 controls (2475 men, 1964 women; eGFR, > or =60 ml min(-1) 1.73 m(-2)). The genotypes for 40 polymorphisms of 32 candidate genes were determined. RESULTS: The chi-square test and multivariable logistic regression analysis with adjustment for covariates revealed that the -219G-->T polymorphism of APOE, the -519A-->G of MMP1, the -866G-->A of UCP2, the -1607/1G-->2G of MMP1, the A-->G (Lys45Glu) of MMP3, the G-->A (Ala163Thr) of AGTR1, the G-->A (Gly670Arg) of PECAM1, and the -55C-->T of UCP3 were significantly (false discovery rate <0.05) associated with CKD. Comparison of allele frequencies of these polymorphisms by the chi-square test between subgroups of CKD and control subjects individually matched for covariates revealed that the -519A-->G of MMP1 and the -866G-->A of UCP2 were significantly (P < 0.05) associated with CKD. CONCLUSIONS: MMP1 and UCP2 may be susceptibility loci for CKD in Japanese individuals. Determination of genotypes for these polymorphisms may prove informative for prediction of genetic risk for CKD.