Association of Polymorphisms in Endothelial Nitric Oxide Synthesis and Renin-Angiotensin-Aldosterone System with Developing of Coronary Artery Disease in Bulgarian Patients

Aim: The purpose of this study was to evaluate the association of common polymorphisms in endothelial nitric oxide synthesis (eNOS; G894T) and renin-angiotensin-aldosterone system (angiotensin converting enzyme [ACE]I/D, angiotensinogenT704C, and angiotensin II receptor type 1A1166C) as risk factors in the pathogenesis of coronary artery disease (CAD) in Bulgarian patients. Methods: This study included 171 patients with CAD and 123 control subjects. Polymerase chain reaction-restriction fragment length polymorphism was used for studying the single-nucleotide polymorphisms. Statistical analysis was performed using statistical software PASW for Windows. Results: A significantly higher percentage of the eNOS T894 allele was found in patients with acute coronary syndrome (ACS), compared to controls (p=0.006) and patients with stable angina pectoris (SAP, p=0.005). Results from a binary regression analysis suggested that eNOS T allele and ACE D allele carriers were more likely to develop ACS than controls (T allele odds ratio [OR] 2.585, p=0.024; D allele OR 3.585, p=0.046) and patients with SAP (T allele OR 2.955, p=0.009; D allele OR 2.703, p=0.05). Exploratory evaluation of gene-gene combinations showed a significant association between eNOS-G894T/ACE-I/D and ACS compared to controls (p=0.022) and patients with SAP (p=0.017). Conclusions: The eNOS G894T and ACE I/D polymorphisms are associated with an increased risk of developing ACS after adjusting for classical risk factors for atherosclerosis in the Bulgarian cohort.