Type 2 diabetes significantly modulates the cardiovascular risk conferred by the PAI-1 − 675 4G/5G polymorphism in angiographied coronary patients

• Published in: Clinica chimica acta Vol. 396; no. 1; pp. 18 - 22
• Main Authors: Saely, Christoph H., Muendlein, Axel, Vonbank, Alexander, Sonderegger, Gudrun, Aczel, Stefan, Rein, Philipp, Risch, Lorenz, Drexel, Heinz
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2008
• Subjects: Angiography; Coronary Artery Disease - complications; Coronary Artery Disease - diagnostic imaging; Coronary Artery Disease - epidemiology; Coronary Artery Disease - genetics; Coronary atherosclerosis; Diabetes Complications - diagnostic imaging; Diabetes Complications - epidemiology; Diabetes Complications - genetics; Diabetes Complications - metabolism; Diabetes Mellitus, Type 2 - diagnostic imaging; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - metabolism; Disease-Free Survival; Female; Genetic polymorphism; Genotype; Humans; Male; Middle Aged; Plasminogen activator inhibitor 1; Plasminogen Activator Inhibitor 1 - genetics; Plasminogen Activator Inhibitor 1 - metabolism; Polymorphism, Genetic - genetics; Prospective study; Risk Factors; Type 2 diabetes; Type 2 diabetes; Plasminogen activator inhibitor 1; Coronary atherosclerosis; Prospective study; Genetic polymorphism
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2008.06.015

The association of the − 675 4G/5G polymorphism of the plasminogen activator inhibitor-1 ( PAI-1) gene with cardiovascular disease in patients with type 2 diabetes (T2DM) is unknown. Genotyping was performed in 672 consecutive Caucasian patients undergoing coronary angiography for the evaluation of stable coronary artery disease (CAD). Vascular events were recorded over 4 years. In non-diabetic subjects ( n = 524), the homozygous PAI-1 4G4G genotype was significantly associated with significant coronary stenoses ≥ 50% (adjusted odds ratio (OR) OR = 1.84 [1.17–2.92]; p = 0.009); however, in T2DM patients ( n = 148) no such association was observed (OR = 0.67 [0.26–1.71]; p = 0.401). An interaction term T2DM × 4G4G genotype was significant ( p = 0.006), indicating a significantly stronger association of the polymorphism with CAD in non-diabetic subjects than in patients with T2DM. Also prospectively, the 4G4G genotype conferred an increased risk of vascular events in non-diabetic subjects but not in T2DM patients (hazard ratios 1.76 [1.13–2.74]; p = 0.014 and 0.68 [0.30–1.54]; p = 0.360, respectively). Again, the interaction T2DM × 4G4G genotype was significant ( p = 0.018). Presence of T2DM significantly modulates the vascular risk conferred by the PAI-1 − 675 4G/5G polymorphism in angiographied coronary patients.