Emerging role of genetic variants of matrix metalloproteinases genes in left ventricular dysfunction

Abstract

Heart failure (HF) is defined as inability of the heart to pump sufficient blood to meet the body's metabolic demands. Left ventricular (LV) dysfunction with progressive HF is a condition in which the left ventricle of the heart becomes functionally impaired. The impaired ventricular function can be attributed to unfavourable ventricular remodelling. Among the pathways that contribute to remodelling process, matrix metalloproteinases (MMPs) appear to be of particular interest. It has been established that altered MMP activity under pathological conditions leads to a situation favouring proteolysis that results in adverse ventricular remodelling, leading to LV dilatation, loss of contractile function and progressive clinical heart failure. Therefore, the aim of the work described in this chapter is to explore the role of genetic variants of MMP genes [MMP2 (C-735 T, rs2285053), MMP7 (A-181G, rs11568818) and MMP9 (R279Q, rs17576), (P574R, rs2250889), (R668Q, rs17577)] with LV dysfunction in coronary artery disease (CAD) patients. The study included 510 consecutive patients with angiographically confirmed CAD. Among patients with CAD, 162 with reduced left ventricle ejection fraction (LVEF <45) were categorised as LVD. The MMP9 R668Q genetic variant was significantly associated with LVD (LVEF <45) (p-value=0.007, OR = 3.48), while no significant difference was observed in the distribution of MMP2 C-735 T, MMP7 A-181G and MMP9 R279Q, P574R genetic variants both at genotype and allele levels. Also the frequency of MMP9279R574P 668Q haplotype comprising MMP9 R668Q variation was significantly higher in reduced LVEF subjects (p-value = 0.008, OR= 1.83). The study concludes that MMP9 R668Q polymorphism plays significant role in conferring genetic susceptibility to left ventricular dysfunction in coronary artery disease patients.