Interferon Regulatory Factor 5 and Renin-Angiotensin-Aldosterone System Polymorphisms in Coronary Artery Disease: An Overview of Experimental and Clinical Studies

Interferon regulatory factor 5 (IRF5) has an important role in the inflammatory process, a fundamental component of coronary artery disease (CAD). Thus, the objective of this study was to evaluate the association of IRF5 polymorphisms with the development of premature CAD (pCAD) and cardiometabolic parameters. IRF5 polymorphisms (rs1874330, rs3778754, rs3757386, rs3757385, rs3807134, rs3807135, and rs6968563) were determined in 1116 pCAD patients and 1003 controls. Polymorphism distribution was similar in patients and controls; however, the haplotype analysis showed five haplotypes with a different distribution. TGCGTCT (OR (odds ratio) = 1.248, p = 0005) and TCTGCCT (OR = 10.73, p < 0.0001) were associated with a high risk, whereas TCCGTCT (OR = 0.155, p < 0.0001), CGCTTTT (OR = 0.108, p < 0.0001), and TCCGCCT (OR = 0.014, p < 0.0001) were associated with a low risk of pCAD. Associations with aspartate aminotransferase, hypertriglyceridemia, magnesium deficiency, triglycerides/HDL-C index, LDL-C, and adiponectin levels were observed in pCAD patients. In controls, associations with hypoalphalipoproteinemia, non-HDL-C, apolipoprotein B, hyperuricemia, TNF-α, IL-6, IL-15, valvular calcification, and subclinical hypothyroidism were observed. In summary, five haplotypes were associated with pCAD, two with high risk and three with low risk. Some IRF5 polymorphisms were associated with cardiometabolic parameters in pCAD patients and control.

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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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