Laboratory for Endocrinology and Metabolism, RIKEN Center for Genomic Medicine, Yokohama, Kanagawa, Japan.
PLoS One. 2013;8(1):e54064. doi: 10.1371/journal.pone.0054064. Epub 2013 Jan 16.
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.
几项连锁分析将糖尿病肾病的易感位点定位在 18 号染色体 q22-q23 上，位于 18 号染色体 q22.3 上的肌肽二肽酶 1 基因 (CNDP1) 内的多态性已被证明与欧洲 2 型糖尿病患者的糖尿病肾病有关。然而，该位点与糖尿病肾病的关联尚未在日本人群中进行评估。在这项研究中，我们检查了 2 型糖尿病日本患者中 CNDP1/CNDP2 基因座内多态性与糖尿病肾病的关联。
方法/主要发现：我们对位于 CNDP1 内的亮氨酸重复多态性 (D18S880) 以及 CNDP1/CNDP2 基因座内的 29 个单核苷酸多态性 (SNP) 进行了基因分型，共纳入 2740 例 2 型糖尿病日本患者（1205 例显性肾病或终末期肾病 [ESRD] 肾病患者，1535 例正常白蛋白尿对照者）。通过逻辑回归分析分析了每个多态性与糖尿病肾病的关系。我们在 2 型糖尿病日本患者中未观察到 D18S880 与糖尿病肾病之间存在任何关联。CNDP1/CNDP2 基因座内的 29 个 SNP 均与糖尿病肾病无关，但随后的性别分层分析显示，CNDP1 中的 1 个 SNP 与女性的糖尿病肾病呈名义相关 (rs12604675-A;p=0.005，优势比 [OR] = 1.76，95%置信区间 [CI]，1.19-2.61)。rs12604675 与显性蛋白尿有关 (p=0.002，OR=2.18，95%CI，1.32-3.60)，但与日本 2 型糖尿病女性的 ESRD 无关。
结论/意义：CNDP1 中的 rs12604675-A 可能使日本 2 型糖尿病女性易患显性蛋白尿。
