The Association between KCNQ1 Gene Polymorphism and Type 2 Diabetes Risk: A Meta-Analysis

BackgroundKCNQ1 (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. MethodsDatabases 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. ResultsA 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 ConclusionsThis meta-analysis suggests that the rs2237892 and rs2237895 polymorphisms in KCNQ1 are associated with elevated type 2 diabetes susceptibility.背景：KCNQ1（钾离子电压门控通道KQT样亚家族成员1）编码电压门控钾通道（KvLQT1）的孔形成亚基，该通道在心肌动作电位复极以及上皮组织的水盐转运过程中发挥关键作用。近期，全基因组关联研究（Genome-Wide Association Studies）已将KCNQ1鉴定为亚洲人群中2型糖尿病（Type 2 Diabetes, T2D）的易感基因。此后，多项研究报道KCNQ1基因的rs2237892与rs2237895多态性与2型糖尿病发病风险相关。但目前关于上述多态性与2型糖尿病的关联研究结果仍存在分歧。为探究这一不一致性，本研究开展了此项荟萃分析（Meta-Analysis）。 方法：检索PubMed、EMBASE、Web of Science及中国知网（China National Knowledge Infrastructure, CNKI）等数据库以获取相关研究。采用比值比（Odds Ratio, OR）及其95%置信区间（Confidence Interval, CI）评估关联强度，通过亚组分析与meta回归分析潜在的异质性来源。 结果：最终纳入25项相关研究，共计70577例2型糖尿病患者与99068例对照。总体而言，C等位基因关联2型糖尿病的合并比值比为1.32（95%置信区间1.26–1.38；P<0.0001）。 结论：本项荟萃分析结果表明，KCNQ1基因的rs2237892与rs2237895多态性与2型糖尿病易感性升高显著相关。