Affiliations: Department of Genetics, Sanjay Gandhi Post Graduate
Institute of Medical Sciences (SGPGIMS), Lucknow, India | Department of Cardiology, Sanjay Gandhi Post Graduate
Institute of Medical Sciences (SGPGIMS), Lucknow, India
Note: [] Corresponding author: Dr. Balraj Mittal (Professor), Department
of Genetics, SGPGIMS, Lucknow-226014 (UP) India. Fax: +91 522 2494322; E-mail:
balraj@sgpgi.ac.in/bml_pgi@yahoo.com
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 and
CYP11B2 T-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), but CYP11B2 (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.
