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

Abstract

Background 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. Methods 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. Results 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). Conclusions Presence of T2DM significantly modulates the vascular risk conferred by the PAI-1 − 675 4G/5G polymorphism in angiographied coronary patients.