Study On The Association Of The Gene Polymorphism And Plasma Level Of Matrix Metalloproteinase-1 And Plasma Level Of Lipoprotein(a) With Acute Coronary Syndrome

BackgroundCoronary atherosclerotic heart disease (CHD) is the most common type of organ damage caused by atherosclerosis.it is also a common diseases that seriously endanger people's health. Acute coronary syndrome (ACS) is a serious type of CHD, it is a public health problem that seriously affect people's physical and mental health in all of the world. In European and American countries,the number of deaths caused by ACS account for about 1/3 of the total number of deaths. In China it has also become one of the most serious epidemic, morbid- dity and mortality rates showed an upward trend year after year, seriously endangering people's health. The pathophysiology of ACS is primarily based on unstable plaque rupture or fracture occurs, Thrombosis formed by platelet aggregation was covered on the plaque which is rupture or fissure, the characteristic of unstable plaque is rich in lipids and fiber cap is thin. matrix metalloproteinase-1(MMP-1) is an interstitial collagenase of the matrix metalloproteinase(MMP) family which can degrade the collagen of extracellular matrix, Lead to fibrous cap of atherosclerotic plaque thinning and easy to rupture, ACS happened. Recent study found that MMP gene polymorphism, lipoprotein (a) [Lp(a)] and many cytokines can regulate MMP expression and activity. Therefore, from the gene,the factors that affect gene expression and the product level of its expressed to study the pathogenesis of the ACS has an important significance to further clarify the pathogenesis of ACS.Objectives1 Detection MMP-1 gene-519A/G polymorphism, and further determination of the plasma level of MMP-1 and Lp (a), research the distribution of MMP-1 gene polymorphi- sms in Han population in Henan Province of China; the relationship between MMP-1 gene polymorphism and its plasma level,Lp (a) and the plasma level of MMP-1.2 To explore the relationship between MMP-1 gene polymorphism and its plasma levels,Lp (a) with the ACS.Methods416 hospitalized patients with CHD was Randomly selected from the department of cardiology in First Affiliated Hospital of Zhengzhou University ,all CHD patients were divided into acute coronary syndrome (ACS) group (295 cases), including 165 cases with unstable angina pectoris (UAP); 130 cases with acute myocardial infarction (AMI); 121 cases with stable angina pectoris (SAP); 236 non CHD patients are excluded by CAG as the control group. All subjects enrolled in the study were unrelated Chinese Han populati- on of Henan Province. Genomic DNA was purified from venous blood.polymerase chain reaction- restriction fragment length polymorphism analysis (PCR-RFLP) methods were used to detect the -519 A/G polymorphism of MMP-1 gene; We randomly selected 53 cases from ACS group,37 cases from SAP group,42 cases from the control group, using enzyme-linked immunosorbent assay (EL1SA) method to determine the plasma level of MMP-1; using immunohistochemical transmission turbidim- etry to determine plasma level of LP (a). Analysis the relationship between MMP-1 gene polymorphism and its plasma levels,Lp (a) and MMP-1; the relationship between MMP-1 gene polym- orphism and its plasma levels,Lp (a) and ACS.Results1 The test results of MMP-1 gene-519A/G polymorphism There were three genotypes of -519A/G in Han People of Henan district:AA AG and GG.The frequency of AA genotype in patients with ACS group was significantly higher than that in SAP group(OR=1.435,95%CI:1.178-1.749, P<0.001) and control group (OR=1.827,95%CI:1.445-2.309, P<0.001).The frequency of A allele in ACS Group was also significantly higher than SAP group(OR=1.407, 95%CI:1.168-1.695, P<0.001) and control group(OR=1.679,95%CI:1.351-2.087, P<0.001).there were no significant difference of AA genotype distribution and the frequency of A allele betw- een AMI group and UAP group, P>0.05.There was no significant relationship between the three kinds of genotypes and the number of diseased vessels,(χ2=2.366, P>0.05).2 Determination results of the plasma level of MMP-1MMP-1 plasma level of ACS group was significantly higher than the control group and SAP group, P<0.05; there were no significant difference of plasma level of MMP-1 between AMI group and UAP group, P>0.05.there were no signif- icant difference of plasma level of MMP-1 between the different genotypes, P>0.05.3 Determination results of the plasma level of LP (a)LP (a) plasma level of ACS group was significantly higher than the control group and SAP group, P<0.05; there were no significant difference of plasma level of LP (a) between AMI group and UAP group, P>0.05.there is a significantly positive correlation between plasma levels of MMP-1 and LP (a) in ACS group, (r=0.408, P<0.01).Conclusion1 There are polymorphisms of -519A/G in Han People of Henan province in MMP-1 gene. The distribution of these gene polymorphisms may exist racial and district differ- entces.2 MMP-1 gene-519A/G polymorphism in Han People of Henan province is related to the pathogenesis of acute coronary syndrome; AA genotype may be a genetic risk factor of acute coronary syndrome.3 The higher plasma level of MMP-1 is associated with the instability of coronary plaque in Han People of Henan province, and it plays a important role in the occurrence of ACS. 4 MMP-1 gene-519A/G polymorphism is not significantly associated with plasma level of MMP-1 in Han people of Henan province.5 There is a strong Positive correlation between plasma levels of MMP-1 and LP (a) in ACS. Show that LP (a) and MMP-1 are interact on each other in the pathogenesis of ACS.