Rose Christian S, Ek Jakob, Urhammer Søren A, Glümer Charlotte, Borch-Johnsen Knut, Jørgensen Torben, Pedersen Oluf, Hansen Torben
Steno Diabetes Center, DK-2820 Gentofte, Denmark.
Diabetes. 2005 Oct;54(10):3026-31. doi: 10.2337/diabetes.54.10.3026.
A graded relationship has been reported between fasting and postprandial plasma glucose levels and the subsequent risk of cardiovascular morbidity and mortality. We hypothesized that the GCK -30G>A promoter polymorphism is associated with elevated glycemia in the middle-aged general population of whites, as well as with features of the World Health Organization (WHO)-defined metabolic syndrome. The GCK -30G>A polymorphism was genotyped in the population-based Inter99 study cohort (5,965 subjects) and in 332 nondiabetic subjects and 1,063 patients with type 2 diabetes. In the Inter99 cohort, the GCK -30A allele was associated with increased fasting (P < 0.001) and post-oral glucose tolerance test (OGTT) plasma glucose levels (P < 0.001), and in the same cohort, the GCK -30A allele was more frequent among 1,325 subjects with the metabolic syndrome than among 1,679 subjects without any components of the metabolic syndrome (P = 0.002). Moreover, the GCK -30A allele frequency was higher among 2,587 subjects with impaired glucose regulation (IGR) than among 4,773 glucose-tolerant subjects (17.3% [95% CI 16.2-18.3] vs. 15.0% [14.3-15.7], P < 0.001, odds ratio GG vs. GA 1.21 [1.08-1.36], GG vs. AA 1.62 [1.17-2.24]). In conclusion, the GCK -30G>A polymorphism associates with elevated fasting and post-OGTT glycemia in the middle-aged general population of whites, as well as with IGR and other features of the WHO-defined metabolic syndrome.
空腹及餐后血糖水平与随后发生心血管疾病的发病率及死亡率之间存在分级关系。我们推测，葡萄糖激酶（GCK）-30G>A启动子多态性与中年白人普通人群血糖升高有关，也与世界卫生组织（WHO）定义的代谢综合征特征有关。在基于人群的Inter99研究队列（5965名受试者）以及332名非糖尿病受试者和1063名2型糖尿病患者中，对GCK -30G>A多态性进行了基因分型。在Inter99队列中，GCK -30A等位基因与空腹血糖升高相关（P<0.001），与口服葡萄糖耐量试验（OGTT）后血浆葡萄糖水平升高相关（P<0.001）。在同一队列中，GCK -30A等位基因在1325名患有代谢综合征的受试者中比在1679名无代谢综合征任何组分的受试者中更常见（P = 0.002）。此外，GCK -30A等位基因频率在2587名糖调节受损（IGR）受试者中高于4773名糖耐量正常受试者（17.3%[95%CI 16.2 - 18.3] vs. 15.0%[14.3 - 15.7]，P<0.001，GG与GA的比值比为1.21[1.08 - 1.36]，GG与AA的比值比为1.62[1.17 - 2.24]）。总之，GCK -30G>A多态性与中年白人普通人群空腹及OGTT后血糖升高有关，也与IGR及WHO定义的代谢综合征的其他特征有关。
