CUHK electronic theses & dissertations collection

Based on previous studies, the increasing prevalence of hypertension may be associated with factors such as obesity, dietary salt and fat intake. This study examined the common biochemical and anthropometric markers that are associated with blood pressure elevation, increasing metabolic and haemodynamic derangement in subjects in Hong Kong, and related those phenotypic markers to some genetic polymorphisms relevant to hypertension.Five hundred and thirty nine Hong Kong Chinese subjects were examined. They were aged from 20 to 60 years, and were hypertensive or normotensive siblings from families with a hypertensive proband, and normotensive controls without a family history of hypertension. The interrelationships between pathophysiological changes and various neurohormones considered relevant to the development of hypertension were investigated. Fasting blood and 24 hour urine samples were collected. Plasma insulin, plasma leptin, plasma renin activity (PRA), serum angiotensin converting enzyme (ACE) activity, aldosterone, 24 hour urine noradrenaline, adrenaline, dopamine and kallikrein were measured. A robust assay for the measurement of urine free cortisol and cortisone and 6beta-hydroxycortisol by an LC-MS/MS method was developed and validated. The ratio between urine free cortisol and cortisone was used as an estimate of the activity of 11beta-hydroxysteroid dehydrogenase type II (11betaHSD2) for cortisol metabolism. These parameters were related to polymorphisms in three genes, the angiotensinogen (AGT) gene M23 5T, the dopamine D1 receptor (DD1R) gene A-48G and the dopamine D2 receptor (DD2R) gene Taq1 A polymorphisms. Analysis of variance was employed for the parameters in the three groups of subjects and for an age-matched sibling pair analysis (using 1 normotensive and 1 hypertensive sibling from each family). Comparisons between parameters were also made after dividing the whole population into 3 groups according to the tertiles of blood pressure. (1) Central (higher waist to hip ratio and waist circumferences) and general (greater body mass index and weight) obesity were found in both hypertensive patients and the normotensive siblings compared to the control subjects. These obesity indices showed strong positive relationships with increased insulin resistance and blood pressure. The obesity indices were also independently associated with systolic and diastolic blood pressure, with central obesity showing the stronger associations. (2) Hypertensives had more adverse lipid profiles, insulin resistance and higher fasting plasma glucose levels. This suggested that the blood pressure elevation in the hypertensives may be mediated through obesity and insulin resistance. (3) Both the hypertensive and normotensive members of sibling pairs had lower noradrenaline and cortisol excretion and higher activity of 11betaHSD2 compared to the normotensive controls. The result showed positive relationships between noradrenaline and increased obesity, insulin resistance and blood pressure, while the relationship between adrenaline and blood pressure was inversed. (4) Lower plasma ACE activity and aldosterone were found in the hypertensives and their siblings than in the normotensive controls. There was a reduction in PRA across the blood pressure tertiles as blood pressure increased. In addition to the higher 11betaHSD2 activity, a negative relationship between aldosterone and blood pressure in hypertensive siblings was observed. These findings may indicate the protective mechanism of these systems in this population. In subjects with the different polymorphisms of AGT M235T, there were no differences in the PRA, serum ACE activity or aldosterone, but lower urine cortisol and kallikrien were found in relation to increasing numbers of the T allele. There was a weak association between the AGT M235T polymorphism and hypertension. (5) Despite the strong correlation of dopamine excretion between hypertensive and normotensive siblings within families, lower dopamine levels were found in the normotensive siblings. A consistent positive relationship was found between urine dopamine and sodium excretion, which supports the concept of the natriuretic effect of dopamine. There was no phenotypic difference found in any of the biochemical parameters in relation to the DDIR A-48G and DD2R Taq1 A polymorphisms, but there were weak associations with blood pressure and these polymorphisms in the sibling study.The normotensive siblings had metabolic abnormalities similar to but less severe than the hypertensive probands, which suggests that the genetic effects and interacting effect of shared lifestyle and environmental factors with their hypertensive family member may be influential on the healthy siblings. Adaptive changes were seen in some of the blood pressure regulating systems in both the hypertensive probands and the normotensive siblings. The major factors predisposing to the hypertension in these subjects appeared to be obesity and insulin resistance and the adaptive changes were insufficient to compensate for these in the hypertensive subjects.Chu Ten Wah Tanya."March 2006."Adviser: Brian Tom Linson.Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1547.Thesis (Ph.D.)--Chinese University of Hong Kong, 2006.Includes bibliographical references (p. 304-341).Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.Abstracts in English and Chinese.School code: 1307