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Association Of Aldosterone Synthase (CYP11B2)-344C/T Gene Polymorphism With Coronary Heart Disease In The Chinese

Posted on:2006-08-30Degree:MasterType:Thesis
Country:ChinaCandidate:W H MengFull Text:PDF
GTID:2144360152493354Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Aldosterone, the principal human mineralocorticoid, one of the main effectors of the renin-angiotensin-aldosterone system, is required for survival by regulating sodium homeostasis and intravascular volume. Researchers now have found that aldosterone can be synthesized not only in the adrenal zona glomerulosa but also in other organs and tissues, such as cardiovascular system, liver, lung, and kidney. These aldosterones play an important role on the remodify and fibrosis of the organs and tissues. More importantly, these aldosterones are involved in the development of vascular inflammation, which is regarded as one of the mechanisms of coronary atherosclerosis.Aldosterone synthase, which has steroid 11 β -hydroxylase activity as well as the 18-hydroxylase and 18-oxidase activities, is responsible for the last step of aldosterone biosynthesis. It is a mitochondrialcytochrome P450 enzyme, encoded by the CYP11B2 gene located on chromosome 8, band q24.3. The CYP11B2 gene consists of almost 7000 base pairs, including 8 introns and 9 exons. Hamph et al identified a total of 13 polymorphisms in the CYP11B2 promoter region. One potentially interesting polymorphism in CYP11B2 is located in the 5' flanking region of the gene, 344 nucleotides upstream from the translation within a binding site for the transcription factor steroidogenic factor-I (SF-I). This position may be either a C or T nucleotide. There is a report that when the position is C allele, the quantity of aldosterone and aldosterone synthase will be decreased.Since aldosterone plays a role in the progress of coronary heart disease (such as vascular in flammation) and this -344C/T gene polymorphism of the CYP11B2 may attect the quantity of aldostrone, the research on the relationship between this polymorphism and coronary heart disease may be worthy.In this study, we investigated the CYP11B2 -344C/T polymorphism using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Our objective is to study the distribution of -344C/T gene polymorphism in Chinese people andits relationship with coronary heart disease (CHD) and myocardial infarction (MI). SUBJECT AND METHODS1. SubjectsControl group: 132 normal subjects (100 men and 32 women, mean aged 64±9 years) served as a control group. None of them had a history of cardiovascular disease or diabetes mellitus. All subjects were Chinese Han nationality. There was no relationship between individuals in the study populationCHD group: 140 patients (99 men and 41 women, mean aged 62±10 years) with CHD disease were consecutively collected from the hospitalized in the department of cardiology, the second affilliated hospital of medical college, Zhejiang University. All patients met the diagnostic criteria for ischemic heart disease by the World Health Organization, 92 patients with MI, all patients were confirmed by coronary angiography.2. Documentation of CHD SeverityThe severity of coronary stenosis was determined by the number of significantly stenosed coronary arteries as follows. Angiograms wereassessed by two cardiologists who were unaware that the patients wereto be included in the study. Each angiogram was classified as revealingeither coronary lesion with more than 50% luminal stenosis or one, two,or three major epicardial coronary arteries with more than 50% luminalobstructions.3. Risk for coronary heart diseaseAll paients with coronary heart disease completed a questionnaire that included demographic data: age, sex, place of birth, hyperlipimia, hypertension, diabetes mellitus, smoking, et al.1. Hyperlipimia was defined as serum total cholesterol (TC) 220mg/dl or more, low-density lipoprotein-cholesterol (LDL) 140mg/dl or more, triglyceride (TG) 150mg/dl or more, high-density lipoprotein-cholesterol (HDL) 35mg/dl or less.2. Hypertension was defined as 140/90 mmHg or more. Both previous medical records of raised blood pressure and present values were collected.3. Diabetes mellitus (DM) were recorded in accordance with 1997 criteria by the Expert Committee...
Keywords/Search Tags:coronary heart disease, myocardial infarction, aldosterone synthase, gene polymorphism
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