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 > or =1 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.
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 > or =1 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.
Authors: N Shaat; E Karlsson; A Lernmark; S Ivarsson; K Lynch; H Parikh; P Almgren; K Berntorp; L Groop Journal: Diabetologia Date: 2006-04-26 Impact factor: 10.122
Authors: Tennille S Leak; Carl D Langefeld; Keith L Keene; Carla J Gallagher; Lingyi Lu; Josyf C Mychaleckyj; Stephen S Rich; Barry I Freedman; Donald W Bowden; Michèle M Sale Journal: BMC Med Genet Date: 2010-02-08 Impact factor: 2.103
Authors: Q Qi; Y Wu; H Li; R J F Loos; F B Hu; L Sun; L Lu; A Pan; C Liu; H Wu; L Chen; Z Yu; X Lin Journal: Diabetologia Date: 2009-02-25 Impact factor: 10.122
Authors: Michael N Weedon; Vanessa J Clark; Yudong Qian; Yoav Ben-Shlomo; Nicholas Timpson; Shah Ebrahim; Debbie A Lawlor; Marcus E Pembrey; Susan Ring; Terry J Wilkin; Linda D Voss; Alison N Jeffery; Brad Metcalf; Luigi Ferrucci; Anna Maria Corsi; Anna Murray; David Melzer; Bridget Knight; Bev Shields; George Davey Smith; Andrew T Hattersley; Anna Di Rienzo; Tim M Frayling Journal: Am J Hum Genet Date: 2006-10-06 Impact factor: 11.025