The Influence of a Single Nucleotide Polymorphism within CNDP1 on Susceptibility to Diabetic Nephropathy in Japanese Women with Type 2 Diabetes

Background Several linkage analyses have mapped a susceptibility locus for diabetic nephropathyto chromosome 18q22–23, and polymorphisms within the carnosine dipeptidase 1gene (CNDP1), located on 18q22.3, have been shown to be associated with diabetic nephropathyin European subjects with type 2 diabetes. However, the association of this locus with diabetic nephropathyhas not been evaluated in the Japanese population. In this study, we examined the association of polymorphisms within the CNDP1/CNDP 2 locus with diabetic nephropathyin Japanese subjects with type 2 diabetes. Methodology/Principal Findings We genotyped a leucine repeat polymorphism (D18S880) that is within CNDP1 along with 29 single nucleotide polymorphisms (SNPs) in the CNDP1/CNDP2 locus for 2,740 Japanese subjects with type 2 diabetes(1,205 nephropathycases with overt nephropathyor with end-stage renal disease [ESRD], and 1,535 controls with normoalbuminuria). The association of each polymorphism with diabetic nephropathywas analysed by performing logistic regression analysis. We did not observe any association between D18S880 and diabetic nephropathyin Japanese subjects with type 2 diabetes. None of the 29 SNPs within the CNDP1/CNDP2 locus were associated with diabetic nephropathy, but a subsequent sex-stratified analysis revealed that 1 SNP in CNDP1 was nominally associated with diabetic nephropathyin women (rs12604675-A; p = 0.005, odds ratio [OR] = 1.76, 95% confidence interval [CI], 1.19−2.61). Rs12604675 was associated with overt proteinuria (p = 0.002, OR = 2.18, 95% CI, 1.32−3.60), but not with ESRD in Japanese women with type 2 diabetes. Conclusions/Significance Rs12604675-A in CNDP1 may confer susceptibility to overt proteinuria in Japanese women with type 2 diabetes.