Font Size: a A A

Association Of Chymase And Renin-angiotensin System Gene Polymorphism With Coronary Heart Disease In The Chinese

Posted on:2004-12-25Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y P ShiFull Text:PDF
GTID:1104360092490610Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
BACKGROUNDCoronary heart disease (CHD) is the one of the main disease to threaten human's health in the present world. In our country, coronary heart disease has been taking on obvious ascending trend and has become the main cause of death in some cities and regions. Hypertension, hyperlipemia, smoking, or diabetes mellitus are well-known risk factors for coronary heart disease . It also is known that a family history of coronary heart disease is a powerful independent coronary risk factor. This illustrates that coronary heart disease may be mutifactorial genetic disease, arise from interactions between envionmental and genetic factors.New molecular biology techniques applied to genetic diagnosis make it possible to study the mechanisms underlying individual and familial predisposition to suffering certain diseases. Specifically, in relation to coronary heart disease, the genetic markers linked to the renin-angiotensin system (RAS) have received special attention, not only because of their well-known effects on vascular homeostasis, but also the promise of the use of angiotensin-converting enzyme inhibitor (ACEI) to reduce morbidity and mortality in coronary heart disease."This project was supported by the Zhejiang Province Program for key Science and Technology (No.021103166) , Zhejiang Province Foundation of Medicine and Sanitation (No.2000A101)The findings that relate RAS genes to coronary heart disease are recent and several polymorphisms in different genes of this system have been described. I/D polymorphism of the gene that codes for ACE consists of the presence (I) or absence (D) of 287 base pairs in intron 16 of the gene. The D allele is accompanied by higher plasma and tissue concentrations of ACE activity than the I allele, which could provide a pathophysiological explanation for the higher incidence of myocardial infarction (MI) and coronary heart disease in individuals with the DD genotype. Various studies have tried to confirm these observations, with debatable results. Our early study clued to that the ACE gene deletion polymorphism is associated with in the occurrence of coronary heart disease and myocardial infarction in the population of Chinese.The angiotensinogen(AGT) gene, a second component of the RAS, has been related with the progression of heart disease. A polymorphism in exon 2 of the gene, consisting of the substitution of methionine by treonine in position 235 of the coded protein (M235T) has been associated with higher AGT concentrations and higher blood pressure. A study reported an association between the TT genotype and increased risk of coronary heart disease, independently of the presence of hypertension.A third component of the RAS is the gene of the angiotensin- n type 1 receptor (ATjR). Most of the effects of angiotensin (Ang) II are mediated through ATiR.A polymorphism of AT]R A1166C has been identified in region 3' of the gene that corresponds with an A→C substitution in messenger RNA. The association between this polymorphism and coronary heart disease has been analyzed by different groups.Another area that remains to be explored is the relevance of human heart chymase (CMA) gene in any effects on coronary heart disease . Human heart CMA has regional differences in its cardiac expression and is a more potent local converter of Ang I to Ang n than ACE. Production of Ang n by these non-RAS alternative pathways is not inhibited by therapy with ACE inhibitors. A study reported CMA allele G may be a genetic risk factor for atherosclerosis in venouscoronary artery bypass grafts.In this study we examined the classic risk factors and various gene polymorphisms of the RAS and CMA that may explain the high incidence of coronary heart disease and myocardial infarction hi the Chinese Han nationality.SUBJECT AND METHODS1. SubjectsThree hundred and fifty -three patients (277 men and 76 women, mean aged 62?.73 years) with CHD disease were consecutively collected from the hospitalized in the department of cardiology, the second affilliated hospit...
Keywords/Search Tags:Renin-angiotensin
PDF Full Text Request
Related items