Laboratory for Endocrinology andMetabolism, RIKEN Center for GenomicMedicine, Yokohama, Japan.
Diabetes Care. 2010 Apr;33(4):842-6. doi: 10.2337/dc09-1933. Epub 2010 Jan 7.
Genetic factors have been considered to contribute to the development and progression of diabetic nephropathy. The KCNQ1 gene (potassium voltage-gated channel, KQT-like subfamily, member 1) was originally identified as a strong susceptibility gene for type 2 diabetes in two Japanese genome-wide association studies. In this study, we examined the association of single nucleotide polymorphisms (SNPs) within KCNQ1 with diabetic nephropathy in Japanese subjects with type 2 diabetes.
We genotyped 33 SNPs in KCNQ1 using 754 type 2 diabetic patients with overt nephropathy and 558 control subjects (an initial study), and we further examined the association of a candidate SNP using three other independent Japanese populations (replications 1-3).
We found that five SNPs were nominally associated with diabetic nephropathy, and the association of rs2237897 was the strongest. We also found that the T allele frequencies of rs2237897 were consistently higher in the nephropathy groups than in the control groups for all study populations (initial study: 0.33 vs. 0.27; replication 1: 0.32 vs. 0.30; replication 2: 0.33 vs. 0.28; and replication 3: 0.32 vs. 0.28), although the individual associations did not reach statistically significant levels. Combined analysis by a meta-analysis revealed that the T allele of rs2237897 was significantly associated with susceptibility to diabetic nephropathy in Japanese subjects with type 2 diabetes (odds ratio 1.22 [95% CI 1.10-1.34], P = 3.1 x 10(-4), corrected P = 0.01).
These results suggest that KCNQ1 is a new candidate gene for conferring susceptibility to diabetic nephropathy.
遗传因素被认为与糖尿病肾病的发生和进展有关。KCNQ1 基因（钾电压门控通道，KQT 样亚家族，成员 1）最初在两项日本全基因组关联研究中被确定为 2 型糖尿病的一个强易感基因。在这项研究中，我们检查了 KCNQ1 内单核苷酸多态性（SNP）与日本 2 型糖尿病患者糖尿病肾病的关系。
我们使用 754 例显性肾病的 2 型糖尿病患者和 558 例对照（初始研究），对 KCNQ1 中的 33 个 SNP 进行了基因分型，并进一步使用另外三个独立的日本人群（复制 1-3）来检验候选 SNP 的关联。
我们发现有 5 个 SNP 与糖尿病肾病呈名义相关，其中 rs2237897 的相关性最强。我们还发现，在所有研究人群中，rs2237897 的 T 等位基因频率在肾病组中始终高于对照组（初始研究：0.33 对 0.27；复制 1：0.32 对 0.30；复制 2：0.33 对 0.28；复制 3：0.32 对 0.28），尽管个体相关性没有达到统计学显著水平。Meta 分析的综合分析表明，rs2237897 的 T 等位基因与日本 2 型糖尿病患者糖尿病肾病的易感性显著相关（比值比 1.22 [95%CI 1.10-1.34]，P = 3.1 x 10(-4)，校正 P = 0.01）。
这些结果表明 KCNQ1 是一个新的候选基因，可导致糖尿病肾病的易感性。
