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Background  Several linkage analyses have mapped a susceptibility locus for diabetic nephropathy to chromosome 18q22–23, and polymorphisms within the carnosine dipeptidase 1 gene ( CNDP1) , located on 18q22.3, have been shown to be associated with diabetic nephropathy in European subjects with type 2 diabetes. However, the association of this locus with diabetic nephropathy has not been evaluated in the Japanese population. In this study, we examined the association of polymorphisms within the  CNDP1/CNDP 2  locus with diabetic nephropathy in 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 nephropathy cases with overt nephropathy or with end-stage renal disease [ESRD], and 1,535 controls with normoalbuminuria). The association of each polymorphism with diabetic nephropathy was analysed by performing logistic regression analysis. We did not observe any association between D18S880 and diabetic nephropathy in 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 nephropathy in 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.

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