Association of Matrix Metalloproteinase-2 Gene Promoter Polymorphism and the Associated Phenotype Variation with Myocardial Infarction

Abstract

In many developing countries Myocardial infarction has Becoming a major problem in public health 1,2. MI is a multifactorial Disease caused by genetic and environmental factors.The major cause of Death in the world is Myocardial infarction 3. The high plasma lipid Levels, high plasma glucose levels,high blood pressure, obesity, smoking, And family history of cardiac disease are the most important risk factors For MI. MI is mainly due to atherosclerosis of the coronary arteries . The structural changes, which permits the accumulation of cells, Extracellular matrix and lipids in the intimate layer of the diseased artery And allows the growth of atherosclerotic plaque. The fibrous cap lining Atheromatous plaque gets ruptured, gives rise to thrombosis, and its Complications4. Pathophysiology of MI involves a wide variety of proteins, Including the matrix metalloproteinases (mmps).Atheromatous plaque Formation is facilitated by the action of mmps. Major extra cellular Components of the basal lamina around blood vessels such as type 1V Collagen, laminin, and fibronectin are degraded by MMP-2. Mmps Also weakens the arterial wall, resulting destabilizing of atheromatous Plaque and dissolution of fibrous cap leading to MI5. Matrix metalloproteinases are zinc dependent endopeptidases That degrade components of the extracellular matrix (ECM). 72kda type IV collagenase also known as MMP-2, is an ubiquitous Metalloproteinase involved in various functions such as vascular Remodeling, atheromatous plaque rupture, and degrading matrix Proteins. MMP-2, also known as gelatinase A . In human, it is Encoded by the MMP-2 gene6. MMP-2 is produced as zymogen, after the production pro MMP- 2 is thought to be bound to its specific inhibitor, called as tissue Inhibitor of matrix metalloproteinases-2 . There are several pathways for Activation of the proenzyme, but mainly the most important pathway is Activation by membrane type metalloproteinases-1 (MT1-MMP)7. MTIMMP Binds to TIMP-2,this complexed structure comes near to the Active site of the MT-MMP enzyme. This results to removal of two Specific pro peptides from pro MMP-2 and the production of an Active 72 kda MMP-2 enzyme8. The gene for human MMP-2 contains 27,862 basepair genomic DNA and is composed of 13 exons. It has been localized on chromosome 16q219. Several common restriction fragment length polymorphisms (rflps) have been reported in the MMP-2 gene locus. MMP-2 gene – 1306C>T promoter region is linked with development of MI10. This Base transition is situated in CCACC box of the sp1 binding site. Increased MMP-2 levels have been found in the plasma of Patients with MI11. Elevated MMP-2 has also been found in Atherosclerotic plaques of coronary arteries12. In view of this we have evaluated the distribution of MMP-2 Promoter gene polymorphism by PCR- RFLP and the concerned Phenotype (MMP-2) was analyzed by using ELISA.