Abstract
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.
Highlights
Coronary artery disease (CAD) is a complex, multifactorial disease, influenced by pathophysiologic conditions as well as by genetic and environmental factors [1]
There was no significant difference in the mean age of coronary artery disease (CAD) patients and controls
In the present study we used the candidate gene approach to determine whether the genetic variants of renin-angiotensinaldosterone system (RAAS) genes – angiotensin I converting enzyme (ACE), angiotensin II type1 (AT1) and CYP11B2, being important effectors of the renin-angiotensin-aldosterone system, are involved in LV dysfunction in CAD patients
Summary
Coronary artery disease (CAD) is a complex, multifactorial disease, influenced by pathophysiologic conditions as well as by genetic and environmental factors [1]. The major complication that some CAD patients face over time is the impairment in left ventricular function, followed by fall in cardiac output. LVD is defined as a syndrome that develops in response to an ischemic insult, resulting in decline in the pumping capacity of the heart This is characterized by the continuous interactions between the underlying myocardial dysfunction and subsequent compensatory neurohumoral mechanisms that are activated [3]. Mishra et al / RAAS gene polymorphism in LVD attention has been focused on the renin-angiotensinaldosterone system (RAAS) [4] This system is initially able to compensate for the depressed myocardial function and preserve the cardiovascular homeostasis. Left ventricular dysfunction (LVD), followed by fall in cardiac output is one of the major complications in some coronary artery disease (CAD) patients. Conclusion: AT1 A1166C plays important role in conferring susceptibility of LVD
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