Cellular, and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Prevention of Metabolic Disorder Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Sci Rep. 2022 Dec 1;12(1):20709. doi: 10.1038/s41598-022-24931-x.
Due to the central role in insulin secretion, the potassium inwardly-rectifying channel subfamily J member 11 (KCNJ11) gene is one of the essential genes for type 2 diabetes (T2D) predisposition. However, the relevance of this gene to T2D development is not consistent among diverse populations. In the current study, we aim to capture the possible association of common KCNJ11 variants across Iranian adults, followed by a meta-analysis. We found that the tested variants of KCNJ11 have not contributed to T2D incidence in Iranian adults, consistent with similar insulin secretion levels among individuals with different genotypes. The integration of our results with 72 eligible published case-control studies (41,372 cases and 47,570 controls) as a meta-analysis demonstrated rs5219 and rs5215 are significantly associated with the increased T2D susceptibility under different genetic models. Nevertheless, the stratified analysis according to ethnicity showed rs5219 is involved in the T2D risk among disparate populations, including American, East Asian, European, and Greater Middle Eastern, but not South Asian. Additionally, the meta-regression analysis demonstrated that the sample size of both case and control groups was significantly associated with the magnitude of pooled genetic effect size. The present study can expand our knowledge about the KCNJ11 common variant's contributions to T2D incidence, which is valuable for designing SNP-based panels for potential clinical applications in precision medicine. It also highlights the importance of similar sample sizes for avoiding high heterogeneity and conducting a more precise meta-analysis.
由于在胰岛素分泌中起着核心作用，钾离子内向整流通道亚家族 J 成员 11（KCNJ11）基因是 2 型糖尿病（T2D）易感性的必需基因之一。然而，该基因与不同人群 T2D 发展的相关性并不一致。在本研究中，我们旨在检测伊朗成年人常见 KCNJ11 变异与 T2D 发病风险的关联，并进行荟萃分析。我们发现，所检测的 KCNJ11 变异并未导致伊朗成年人 T2D 的发病，这与不同基因型个体的胰岛素分泌水平相似。将我们的结果与 72 项符合条件的已发表病例对照研究（41372 例病例和 47570 例对照）进行荟萃分析，结果表明 rs5219 和 rs5215 与不同遗传模型下 T2D 易感性的增加显著相关。然而，根据种族进行的分层分析表明，rs5219 与包括美国、东亚、欧洲和大中东地区在内的不同人群的 T2D 风险有关，但与南亚人群无关。此外，Meta 回归分析表明，病例组和对照组的样本量与汇总遗传效应大小的幅度显著相关。本研究可以扩展我们对 KCNJ11 常见变异与 T2D 发病风险相关性的认识，这对于设计基于 SNP 的面板用于精准医学中的潜在临床应用具有重要价值。它还强调了为避免高度异质性和进行更精确的荟萃分析而进行类似样本量的重要性。
