Department of Endocrinology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 South Wanpin Road, Shanghai, 200032, People's Republic of China.
Mol Biol Rep. 2013 Jun;40(6):3935-42. doi: 10.1007/s11033-012-2470-6. Epub 2013 Jan 10.
Glucokinase regulatory protein (GCKR) which binds to glucokinase (GCK) in the nucleus and inhibits its activity in the presence of fructose-6-phosphate is critical for glucose metabolism. In the past few years, a number of case-control studies have been carried out to investigate the relationship between the GCKR polymorphism and type 2 diabetes (T2D) since it was first identified to be associated with fasting plasma glucose levels, insulin resistance through genome-wide association approach. After that, a number of studies reported that the rs780094 polymorphism in GCKR has been implicated in T2D risk. However, these studies have yielded contradictory results. To investigate this inconsistency, we performed a meta-analysis of 19 studies involving a total of 298,977 subjects for GCKR rs780094 to evaluate its effect on genetic susceptibility for T2D. In a combined analysis, the summary per-allele odds ratio for T2D of the rs780094 polymorphism was 1.11 (95 % CI: 1.07-1.14, P < 10(-5)). Significant results were also observed using dominant (OR = 1.18, 95 % CI: 1.05-1.34, P < 10(-5)) or recessive genetic model (OR = 1.20, 95 % CI: 1.12-1.28, P < 10(-5)). Significant results were found in Asians and Caucasians when stratified by ethnicity. Besides, the polymorphism was found to be significantly associated with increased fasting plasma glucose level. There was strong evidence of heterogeneity, which largely disappeared after stratification by ethnicity. This meta-analysis suggests that the rs780094 polymorphism in GCKR is associated with elevated T2D risk, but these associations vary in different ethnic populations.
葡萄糖激酶调节蛋白（GCKR）在核内与葡萄糖激酶（GCK）结合，并在果糖-6-磷酸存在的情况下抑制其活性，对于葡萄糖代谢至关重要。自通过全基因组关联方法首次发现其与空腹血糖水平和胰岛素抵抗有关以来，在过去的几年中，已经进行了许多病例对照研究，以研究 GCKR 多态性与 2 型糖尿病（T2D）之间的关系。此后，许多研究报告称，GCKR 中的 rs780094 多态性与 T2D 风险相关。然而，这些研究的结果存在矛盾。为了研究这种不一致性，我们对涉及 298977 名受试者的 19 项研究进行了荟萃分析，以评估 GCKR rs780094 对 T2D 遗传易感性的影响。在综合分析中，rs780094 多态性与 T2D 的每等位基因优势比为 1.11（95%CI：1.07-1.14，P<10(-5)）。使用显性（OR=1.18，95%CI：1.05-1.34，P<10(-5)）或隐性遗传模型（OR=1.20，95%CI：1.12-1.28，P<10(-5)）也观察到了显著结果。按种族分层时，在亚洲人和白种人中也观察到了显著结果。此外，该多态性与空腹血糖水平升高显著相关。存在明显的异质性，但按种族分层后，异质性基本消失。这项荟萃分析表明，GCKR 中的 rs780094 多态性与 T2D 风险升高相关，但这些关联在不同种族人群中存在差异。
