Divisions of Nephrology and Transplantation, Mayo Clinic, Phoenix, AZ 85054, USA.
Mol Genet Metab. 2011 Jun;103(2):185-90. doi: 10.1016/j.ymgme.2011.02.010. Epub 2011 Feb 19.
CNDP1 is located on 18q22.3, where linkage with diabetic nephropathy has been observed in several populations, including Pima Indians. However, evidence for association between CNDP1 alleles and diabetic nephropathy is equivocal and population-dependent. This study investigated CNDP1 as a candidate for diabetic kidney disease in Pima Indians. Nineteen tag single nucleotide polymorphisms spanning the CNDP1 locus were selected using genotype data from Chinese individuals in the HapMap resource along with 2 variants previously associated with diabetic nephropathy. All variants were genotyped in 3 different samples including a diabetic end-stage renal disease (ESRD) case-control study, a family-based study of diabetic individuals who participated in the linkage study for nephropathy, and a cohort of diabetic individuals in whom longitudinal measures of glomerular filtration rates (GFR) were performed. There was no statistically significant evidence for association with diabetic ESRD. However, nominal evidence for association was found in the family study, where markers rs12957330 (Odds ratio [OR]=0.29 per copy of G allele; p=0.04) and rs17817077 (OR=0.46 per copy of G allele; p=0.05) were associated with diabetic nephropathy. In addition, markers rs12964454, rs7244647, and rs7229005 were associated with changes in GFR (-8.5ml/min per copy of the G allele; p=0.04; 18.8ml/min per copy of the C allele; p=0.03; and -13.4ml/min per copy of the C allele; p=0.001, respectively). These findings provide nominal evidence supporting a role between CNDP1 variants and diabetic kidney disease.
CNDP1 位于 18q22.3 上，在包括皮马印第安人在内的几个人群中，已经观察到该区域与糖尿病肾病的连锁。然而，CNDP1 等位基因与糖尿病肾病之间的关联证据存在争议，且具有人群依赖性。本研究调查了 CNDP1 作为皮马印第安人糖尿病肾病的候选基因。使用 HapMap 资源中中国个体的基因型数据以及先前与糖尿病肾病相关的 2 个变体，选择了跨越 CNDP1 基因座的 19 个标签单核苷酸多态性。所有变体均在 3 个不同样本中进行了基因分型，包括糖尿病终末期肾病（ESRD）病例对照研究、参与肾病连锁研究的糖尿病个体的基于家族的研究以及对糖尿病个体进行肾小球滤过率（GFR）纵向测量的队列。没有统计学上的证据表明与糖尿病 ESRD 有关。然而，在家族研究中发现了与名义上的关联，其中标记物 rs12957330（G 等位基因每拷贝的比值比 [OR]=0.29；p=0.04）和 rs17817077（G 等位基因每拷贝的比值比 [OR]=0.46；p=0.05）与糖尿病肾病有关。此外，标记物 rs12964454、rs7244647 和 rs7229005 与 GFR 的变化有关（G 等位基因每拷贝减少 8.5ml/min；p=0.04；C 等位基因每拷贝增加 18.8ml/min；p=0.03；C 等位基因每拷贝减少 13.4ml/min；p=0.001）。这些发现提供了名义上的证据，支持 CNDP1 变体与糖尿病肾病之间存在关联。
