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Association Between A Polymorphism Of The Aldosterone Synthase Gene And Essential Hypertension

Posted on:2005-07-21Degree:MasterType:Thesis
Country:ChinaCandidate:D ChenFull Text:PDF
GTID:2144360125462745Subject:Internal Medicine
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Essential hypertension (EH) is a complex disorder, a risk factor for the coronary heart disease (CHD) and stroke, epidemiological study presents its morbidity becaming higher in past decade. Essential hypertension is a quantitative multifactorial trait influenced by environmental and genetic determinants. For example, offsprings of hypertensive parents have a significant predisposition to hypertension. Essential hypertension is thought to be a polygenic disease. The rennin –angiotensin -aldosterone system (RAS) is a key mechanism in the regulation of blood pressure. Genes that affect the RAS are attractive candidate genes, and nearly all accessible genes have been analyzed extensively. Many gene polymorphisms have been proposed as possible markers for hypertension, including insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene, A1166C polymorphism of the angiotensin II type I receptor gene, and M235T angiotensinogen polymorphism. Recent studies in humans have drawn attention to genes that influence renal sodium handling. Components of the renin-angiotensin system and factors that affect regulation of secretion and action of aldosterone are strong contenders. Among these candidate genes, CYP11B2 gene C-344T polymorphisms has been studied . Some investigators demonstrated a positive association between CYP11B2 gene C-344T polymorphism and increased plasma aldosterone level in essential hypertension. We investigate the association between the polymorphism of aldosterone synthase(CYP11B2)and essential hypertension(EH)and left ventricular hypertrophy(LVH)in population of Dalian. Method 339 outpatients with essential hypertension were enrolled according to the criteria of WHO or were on antihypertensive therapy, secondary hypertension was excluded, 176men and 163women, age from 25 to 93 years and average age 58.5±13.0 years. 640 healthy people were enrolled into this study, who had systolic and diastolic blood pressures of <140/90 mm Hg and absence of antihypertensive treatment, 396men and 244women, age from 20 to 94 years and average age was 43.1±11.2 years. All patients' sitting blood pressure were measured, M-mode echocardiogram were performed on 150 patients, left ventricular mass (LVM) and left ventricular mass index (LVMI) were calculated according to the formula described by Devereux et al. Genome DNA was extracted from white blood cell. Polymerase chain reaction (PCR) and restriction fragment-length polymorphism (RFLP) were employed to study C-344T polymorphism of CYP11B2 gene. The frequencies of genetype and allele in two groups were compared byχ2 test. Anthropometric and echocardiographic data were compared by ANOVA. The association between genetype and essential hypertension was analyzed by Logistic analysis, age, sex, BMI and family history were included.Result 1.Clinical characteristics and biochemical examinations showed BMI, blood pressure in EH were significantly higher than those in the control. Total cholesterol level was significantly higher and ApoA was lower in hypertensive patients than the control. 2. The frequency of CYP11B2 -344C/T genotype in the hypertensive cohort and controls were CC: 0.07 vs 0.10, CT: 0.43 vs 0.41, TT: 0.50 vs 0.49 respectively; allele frequencies were C: 0.28 vs 0.30, T: 0.72 vs 0.70. There was no significant difference in genotype or allele frequency distribution in the hypertensive group and control group. 3.In sex-specific analyses, the polymorphism of CYP11B2 was associated with IVS only in women. 4.There was no significant difference in genotype or allele frequency distribution in patients with left ventricular hypertrophy and control. 5.Age, sex, BMI and family history were related to EH, OR is 1.593,0.594,1.221,11.453 respectively.Conclusion 1. The polymorphism of the aldosterone synthase gene is not related to essential hypertension .2. The polymorphism of the aldosterone synthase gene is not related to LVH in primary hypertension group, but CC genotype is related to h...
Keywords/Search Tags:aldosterone synthase, essential hypertension, Polymorphism, LVH
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