Department of Endocrinology and Metabolism, Peking University People's Hospital, No. 11 Xi Zhimen Nan Da Jie Main Street, Xi Cheng District, Beijing, 100044, China.
Mol Biol Rep. 2012 Jan;39(1):645-59. doi: 10.1007/s11033-011-0782-6. Epub 2011 May 15.
A number of studies have been performed to identify the association between potassium inwardly-rectifying channel, subfamily J, member 11 (KCNJ11) gene and type 2 diabetes mellitus (T2DM) in East Asian populations, with inconsistent results. The main aim of this work was to evaluate more precisely the genetic influence of KCNJ11 on T2DM in East Asian populations by means of a meta-analysis. We identified 20 articles for qualitative analysis and 16 were eligible for quantitative analysis (meta-analysis) by database searching up to May 2010. The association was assessed under different genetic models, and the pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. The allelic and genotypic contrast demonstrated that the association between KCNJ11 and T2DM was significant for rs5210. However, not all results for rs5215 and rs5218 showed significant associations. For rs5219, the combined ORs (95% CIs) for allelic contrast, dominant and recessive models contrast (with allelic frequency and genotypic distribution data) were 1.139 (1.093-1.188), 1.177 (1.099-1.259) and 1.207 (1.094-1.332), respectively (random effect model). The analysis on the most completely adjusted ORs (95% CIs) by the covariates of rs5219 all presented significant associations under different genetic models. Population-stratified analysis (Korean, Japanese and Chinese) and sensitivity analysis verified the significant results. Cumulative meta-analysis including publication time and sample size illustrated the exaggerated genetic effect in the earliest studies. Heterogeneity and publication bias were assessed. Our study verified that single nucleotide polymorphisms (SNPs) of KCNJ11 gene were significantly associated with the risk of T2DM in East Asian populations.
许多研究已经在东亚人群中进行，以确定钾内向整流通道亚家族 J 成员 11（KCNJ11）基因与 2 型糖尿病（T2DM）之间的关联，但结果不一致。本研究的主要目的是通过荟萃分析更精确地评估 KCNJ11 基因对东亚人群 T2DM 的遗传影响。通过数据库检索，我们在截至 2010 年 5 月的时间内确定了 20 篇文章进行定性分析，其中 16 篇符合定量分析（荟萃分析）的标准。在不同的遗传模型下评估了相关性，并计算了合并的优势比（OR）及其 95%置信区间（95%CI）。等位基因和基因型对比表明，KCNJ11 与 T2DM 之间的关联在 rs5210 上是显著的。然而，并非所有 rs5215 和 rs5218 的结果均显示出显著的相关性。对于 rs5219，等位基因对比、显性和隐性模型对比（基于等位基因频率和基因型分布数据）的合并 OR（95%CI）分别为 1.139（1.093-1.188）、1.177（1.099-1.259）和 1.207（1.094-1.332）（随机效应模型）。基于 rs5219 的协变量对最完全调整的 OR（95%CI）进行的分析，在不同的遗传模型下均呈现出显著的相关性。基于人群的分层分析（韩国人、日本人、中国人）和敏感性分析验证了这些显著的结果。包含发表时间和样本量的累积荟萃分析表明，早期研究中存在夸大的遗传效应。评估了异质性和发表偏倚。我们的研究证实，KCNJ11 基因的单核苷酸多态性（SNP）与东亚人群 2 型糖尿病的风险显著相关。
