Association of matrix metalloproteinases (MMP2, MMP7 and MMP9) genetic variants with left ventricular dysfunction in coronary artery disease patients

Background: Left ventricular dysfunction (LVD) is a condition resulting from clustered structural or functional cardiac disorder that reduces the ability of the ventricle to fill with or eject blood. The impaired ventricular function can be attributed to unfavorable ventricular remodeling. Among the pathways that contribute to remodeling process, matrix metalloproteinases (MMPs) appear to be of particular interest. We explored the association of MMP2 (C-735T, rs2285053), MMP7 (A-181G, rs11568818) and MMP9 (R279Q rs17576), (P574R, rs2250889), (R668Q rs17577) genetic variants with LVD in coronary artery disease (CAD) patients. Methods: The study included 310 consecutive patients with angiographically confirmed CAD and 230 healthy controls. Among patients with CAD, 95 with reduced left ventricle ejection fraction (LVEF <= 45) were categorized as LVD. Polymorphisms were determined by PCR-RFLP. Results: The MMP9 R668Qgenetic variant was significantly associated with LVD (LVEF <= 45) (p value=0.009; OR=3.82). 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=0.033; OR=3.59). Also the frequency of haplotype R,P,Q comprising R668Q variation in MMP 9 was significantly higher in reduced LVEF subjects (p value=0.008; OR=1.83). Conclusion: MMP9 R668Q plays important role in conferring susceptibility of LVD. (C) 2012 Elsevier B.V. All rights reserved.