The Association between PAI-1 Gene Promoter Polymorphism and Serum Serpin E1, MDA, and Hs-CRP Levels in Coronary Artery Disease

Abstract

A B S T R A C TBackground: Coronary artery disease (CAD) caused by atherosclerosis. Studies have shown that there are a number of factors which are closely related to the development and progression of CAD that include Cellular binding molecules like Plasminogen Activator Inhibitor-1(PAI-1), Lipid peroxidation, inflammation and hemostasis. Objectives: The present case-control study aimed to evaluate the association between Plasminogen Activator Inhibitor-1 (PAI-1) 4G/5G polymorphism and oxidative stress markers and Coronary Artery Disease (CAD). Patients and Methods: Blood was drawn and DNA was extracted from 90 subjects (46 patients with angiographically diagnosed CAD and 44 age-and sex-matched healthy controls). The 4G/5G polymorphism of PAI-1 was detected by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) analysis. Besides, the risk factors, serpin E1, Malondialdehyde (MDA), high-sensitivity C-Reactive Protein (hs-CRP), and lipid profile serum levels were measured by standard methods and were compared between the two study groups using independent samples t-test, one-way ANOVA, and Mann-Whitney U test as appropriated. Results: Results: The frequency of 4G/4G genotype of PAI-1 gene was higher in the CAD patients than in the controls (28/46 (60.87%) vs. 8/44 (18.18%), P < 0.01). Additionally, the serpin E1 plasma level was significantly higher in the CAD group carrying the 4G allele compared to those homozygous for the 5G allele (P = 0.016). Besides, a significant difference was found between the 4G/4G and 5G/5G subjects of the CAD group regarding plasma High-Density Lipoprotein (HDL) (P < 0.01). Also, significant differences were observed among the three genotypes of both groups concerning the plasma levels of cholesterol, triglyceride, and Low-Density Lipoprotein (LDL). However, no significant correlation was found between PAI-1 gene polymorphism and MDA serum level, hs-CRP, and risk of CAD. Conclusion: The findings of this study suggested that 4G/4G PAI-1 polymorphism was associated with cholesterol, triglyceride, LDL, and HDL levels and could be regarded as a biomarker for risk of CAD. Our findings suggested that the 4G/5G polymorphism of the PAI-1 gene seems to be a useful marker of fibrinolytic activity. Besides, this polymorphism might contribute to defective fibrinolytic activity due to elevated PAI-1 plasma level, eventually increasing the risk of coronary artery disease. Moreover, the study results demonstrated that this genetic variation might be important in correlation with some other factors, such as increased or decreased triglyceride, cholesterol, and LDL and HDL levels. However, no significant correlation was observed between PAI-1 4G/5G gene polymorphism and serum levels of stress oxidative factors, such as MDA and hs-CRP.