The Synergistic Effect of Plasminogen Activator Inhibitor-1 (PAI-1) Polymorphisms and Metabolic Syndrome on Coronary Artery Disease in the Korean Population

Abstract

The most common type of cardiovascular disease is coronary artery disease (CAD), in which a plaque builds up inside the coronary arteries that can lead to a complete blockage of blood flow to the heart, resulting in a heart attack. The CAD may be affected by various factors including age, gender, and lipoprotein disposition as well as genetic factors and metabolic syndrome. In this study, we investigated whether three PAI-1 polymorphisms (−844 G > A, −675 4G > 5G, and +43 G > A) and CAD-related clinical parameters are associated with CAD susceptibility. Genotyping of 463 CAD patients and 401 controls was performed using polymerase chain reaction restriction fragment length polymorphism analysis. We report that the 4G5G genotype (crude odds ratio(COR), 1.392; 95% confidence interval (CI), 1.036–1.871; p = 0.028) and dominant model (4G4G vs. 4G5G + 5G5G; COR, 1.401; 95% CI, 1.060–1.850; p = 0.018; adjust odds ratio, 1.371; 95% CI, 1.027–1.831; p = 0.032) of PAI-1 −675 polymorphisms were associated with increased CAD risk. Haplotype and genotype combinations of PAI-1 −675 and +43 polymorphisms show an increased risk of CAD according to alterations of the −675 polymorphism allele or genotype. Moreover, the PAI-1 -675 polymorphisms show a synergistic effect with the metabolic syndrome component of CAD risk. This study suggests that polymorphisms in the PAI-1 genes along with the metabolic syndrome component of CAD can be useful biomarkers for CAD diagnosis and treatment.