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

Abstract Background: Hyperhomocysteinemia is an independent, graded risk factor for coronary artery disease (CAD). The G894T variant of endothelial nitric oxide synthase (eNOS) was postulated to be associated with hyperhomocysteinemia and could influence individual susceptibility to CAD. The aims of this study were to investigate (a) the relationship of the eNOS G894T polymorphism with the presence and the severity of CAD and (b) the possible relationship between hyperhomocysteinemia and the eNOS G894T variant for the risk of CAD severity in a Tunisian population. Methods: We used PCR with restriction fragment length polymorphism analysis to detect the G894T variant of the eNOS gene in 100 patients with CAD and 120 healthy controls. The severity of CAD was expressed by the number of affected vessels. Total plasma homocysteine concentrations were determined by direct chemiluminescence assay. Results: The frequencies of the eNOS GG, GT, and TT genotypes in the CAD group were significantly different from those in the control group (45%, 44%, and 11% vs 60%, 35.8% and 4.2%, respectively; P = 0.035). There was no association between the eNOS G894T genotype frequencies and the number of stenosed vessels (P = 0.149). In the CAD group, the coexistence of the 894 GT or TT genotypes and hyperhomocysteinemia led to an increased risk of CAD severity. Conclusion: The G894T polymorphism of the eNOS gene is associated with the presence of CAD, and in conjunction with hyperhomocysteinemia, increased the risk of CAD severity in a Tunisian population.

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Impact of Renin-Angiotensin-Aldosterone System Gene Polymorphisms on Left Ventricular Dysfunction in Coronary Artery Disease Patients

Disease Markers ◽

10.1155/2012/854150 ◽

2012 ◽

Vol 32 (1) ◽

pp. 33-41 ◽

Cited By ~ 13

Author(s):

Avshesh Mishra ◽

Anshika Srivastava ◽

T. Mittal ◽

N. Garg ◽

B. Mittal

Keyword(s):

Coronary Artery Disease ◽

Cardiac Output ◽

Coronary Artery ◽

Left Ventricular Dysfunction ◽

Ventricular Dysfunction ◽

Left Ventricular ◽

P Value ◽

Renin Angiotensin Aldosterone System ◽

Renin Angiotensin ◽

Artery Disease

Background: Left ventricular dysfunction (LVD), followed by fall in cardiac output is one of the major complications in some coronary artery disease (CAD) patients. The decreased cardiac output over time leads to activation of the renin-angiotensin-aldosterone system which results in vasoconstriction by influencing salt-water homeostasis. Therefore, the purpose of the present study was to explore the association of single nucleotide polymorphisms (SNPs) in angiotensin I converting enzyme;ACE(rs4340), angiotensin II type1 receptor; AT1 (rs5186) and aldosterone synthase;CYP11B2(rs1799998) with LVD.Methods and results: The present study was carried out in two cohorts. The primary cohort included 308 consecutive patients with angiographically confirmed CAD and 234 healthy controls. Among CAD, 94 with compromised left ventricle ejection fraction (LVEF ≤ 45) were categorized as LVD. The ACE I/D, AT1 A1166C andCYP11B2T-344C polymorphisms were determined by PCR. Our results showed that ACE I/D was significantly associated with CAD but not with LVD. However, AT1 1166C variant was significantly associated with LVD (LVEF ≤ 45) (p value=0.013; OR=3.69), butCYP11B2(rs1799998) was not associated with either CAD or LVD. To validate our results, we performed a replication study in additional 200 cases with similar clinical characteristics and results again confirmed consistent findings (p value=0.020; OR=5.20).Conclusion: AT1 A1166C plays important role in conferring susceptibility of LVD.

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