Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
PLoS One. 2012;7(11):e48578. doi: 10.1371/journal.pone.0048578. Epub 2012 Nov 2.
KCNQ1 (potassium voltage-gated channel KQT-like sub-family, member 1) encodes a pore-forming subunit of a voltage-gated K(+) channel (KvLQT1) that plays a key role for the repolarization of the cardiac action potential as well as water and salt transport in epithelial tissues. Recently, genome-wide association studies have identified KCNQ1 as a type 2 diabetes (T2D) susceptibility gene in populations of Asian descent. After that, a number of studies reported that the rs2237892 and rs2237895 polymorphism in KCNQ1 has been implicated in T2D risk. However, studies on the association between these polymorphism and T2D remain conflicting. To investigate this inconsistency, we performed this meta-analysis.
Databases including Pubmed, EMBASE, Web of Science and China National Knowledge Infrastructure (CNKI) were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. Potential sources of heterogeneity were also assessed by subgroup analysis and meta-regression.
A total of 25 articles involving 70,577 T2D cases and 99,068 controls were included. Overall, the summary odds ratio of C allele for T2D was 1.32 (95% CI 1.26-1.38; P<10-5) and 1.24 (95% CI: 1.20-1.29; P<10-5) for KCNQ1 rs2237892 and rs2237895 polymorphisms, respectively. Significant results were also observed using co-dominant, dominant and recessive genetic models. After stratifying by ethnicity, sample size, and diagnostic criteria, significant associations were also obtained.
This meta-analysis suggests that the rs2237892 and rs2237895 polymorphisms in KCNQ1 are associated with elevated type 2 diabetes susceptibility.
KCNQ1（钾电压门控通道 KQT 样亚家族，成员 1）编码电压门控 K(+) 通道（KvLQT1）的孔形成亚基，该通道在心脏动作电位复极化以及上皮组织中的水和盐转运中起关键作用。最近，全基因组关联研究将 KCNQ1 鉴定为亚洲人群 2 型糖尿病（T2D）的易感基因。此后，许多研究报告称，KCNQ1 中的 rs2237892 和 rs2237895 多态性与 T2D 风险相关。然而，关于这些多态性与 T2D 之间关联的研究结果仍存在争议。为了探究这种不一致性，我们进行了这项荟萃分析。
我们检索了 Pubmed、EMBASE、Web of Science 和中国知网（CNKI）等数据库，以寻找相关研究。使用比值比（ORs）及其 95%置信区间（CIs）来评估关联的强度。还通过亚组分析和荟萃回归来评估潜在的异质性来源。
共纳入 25 项研究，涉及 70577 例 T2D 病例和 99068 例对照。总体而言，C 等位基因与 T2D 的汇总优势比为 1.32（95%CI 1.26-1.38；P<10-5）和 1.24（95%CI：1.20-1.29；P<10-5），分别对应于 KCNQ1 rs2237892 和 rs2237895 多态性。在共显性、显性和隐性遗传模型中也观察到了显著的结果。按种族、样本量和诊断标准进行分层后，也得到了显著的关联。
这项荟萃分析表明，KCNQ1 中的 rs2237892 和 rs2237895 多态性与 2 型糖尿病易感性升高相关。
