G(-30)A polymorphism in the pancreatic promoter of the glucokinase gene associated with angiographic coronary artery disease and type 2 diabetes mellitus
G(-30)A polymorphism in the pancreatic promoter of the glucokinase gene associated with angiographic coronary artery disease and type 2 diabetes mellitus
复制标题
DOI：
10.1161/01.cir.0000129306.44085.c4
复制
发表时间：
2004-06-15
期刊：
影响因子：
37.8
通讯作者：
Winkelmann, BR
中科院分区：
文献类型：
--
作者：
März, W;Nauck, M;Winkelmann, BR
背景-2型糖尿病（T2DM）增加冠状动脉疾病（CAD）的风险。葡萄糖激酶（GK-30PM）β细胞特异性启动子中的G（-30）A多态性与胰腺β细胞功能降低有关。其对CAD的影响还没有检查。方法和结果-葡萄糖激酶G（-30）A变异体在2567例血管造影CAD患者和731例已被排除CAD血管造影。在A等位基因携带者中，CAD的校正OR为1.39（95%CI，1.15至1.70）。在未患和患T2DM的个体中，相应的OR分别为1.27（95% CI，1.02 - 1.59）和1.92（95% CI，1.26 - 2.93）。A等位基因的患病率与Friesinger冠状动脉评分平行增加。大于或等于1A等位基因携带者更易发生T2DM（OR，1.17; 95% CI，1.00~1.28）。如果仅考虑CAD患者，则这种关联更强。A等位基因与较高的血糖（空腹，P = 0.002;口服葡萄糖后2小时，P = 0.017）和糖化血红蛋白（HbA1c; P = 0.002）相关。此外，1A等位基因的存在与β细胞功能呈负相关，通过β百分比（P = 0.012）和胰岛素原与胰岛素的比率（P = 0.025）以及胰岛素原与C肽的比率（P = 0.019）进行估计。此外，至少在CAD中，它与T2DM的患病率增加相关。
Background - Type 2 diabetes mellitus (T2DM) increases the risk of coronary artery disease ( CAD). A G( -30) A polymorphism in the beta-cell-specific promoter of glucokinase (GK-30PM) has been implicated in reduced pancreatic beta-cell function. Its impact on CAD has not been examined.Methods and Results - The glucokinase G(-30) A variant was determined in 2567 patients with angiographic CAD and in 731 individuals in whom CAD had been ruled out by angiography. In carriers of the A allele, the adjusted OR of CAD was 1.39 (95% CI, 1.15 to 1.70). Corresponding ORs were 1.27 ( 95% CI, 1.02 to 1.59) and 1.92 ( 95% CI, 1.26 to 2.93) in individuals without and with T2DM, respectively. The prevalence of the A allele increased in parallel with the Friesinger coronary score. Patients with T2DM were more frequent among carriers of greater than or equal to1 A allele ( OR, 1.17; 95% CI, 1.00 to 1.28). This association was stronger if CAD patients only were considered. The A allele was associated with higher glucose ( fasting, P = 0.002; 2 hours after oral glucose, P = 0.017) and glycohemoglobin ( HbA1c; P = 0.002). Furthermore, presence of 1 A allele was negatively related to beta-cell function, estimated by beta percent ( P = 0.012) and by the ratios of proinsulin to insulin ( P = 0.025) and proinsulin to C peptide ( P = 0.019).Conclusions - The A allele of the pancreatic promoter of glucokinase increases the risk of CAD in individuals with and without T2DM. Furthermore, at least in CAD, it is associated with an augmented prevalence of T2DM.