Fang Yujing. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (leaves 148-182). / Abstracts in English and Chinese. / Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Overview of the study --- p.1 / Chapter 1.2 --- Overview of Hypertension --- p.4 / Chapter 1.3 --- Overview of Obesity-Related Hypertension --- p.9 / Chapter 1.3.1 --- Body fat distribution --- p.11 / Chapter 1.3.2 --- Insulin resistance and Hyperinsulinaemia --- p.12 / Chapter 1.3.3 --- Sympathetic nervous system activity --- p.13 / Chapter 1.3.4 --- Genetics of Obesity --- p.15 / Chapter 1.3.4.1 --- Brown adipose tissue (BAT) --- p.15 / Chapter 1.3.4.2 --- Uncoupling protein --- p.16 / Chapter 1.3.4.3 --- Uncoupling Protein 1 Gene --- p.17 / Chapter 1.3.4.4 --- Association of the UCP1 Polymorphism and Weight Gain in Obesity --- p.18 / Chapter 1.4 --- Overview of Genetics of Hypertension --- p.19 / Chapter 1.4.1 --- The Renin-Angiotensin System --- p.19 / Chapter 1.4.1.1 --- Functions of Renin-Angiotensin System --- p.20 / Chapter 1.4.1.2 --- The Renin-Angiotensin System and Hypertension --- p.21 / Chapter 1.4.2 --- Renin --- p.22 / Chapter 1.4.3 --- Angiotensinogen --- p.25 / Chapter 1.4.4 --- Angiotensin-Converting Enzyme (ACE) --- p.29 / Chapter 1.4.4.1 --- Angiotensin-Converting Enzyme Gene --- p.29 / Chapter 1.4.4.2 --- Association of the ACE I/D Polymorphism with Hypertension --- p.30 / Chapter 1.4.4.3 --- Association of the ACE I/D Polymorphism with Other disease --- p.32 / Chapter 1.4.5 --- The Angiotensin II Receptor --- p.35 / Chapter 1.4.5.1 --- Type 1 Angiotensin II Receptor --- p.35 / Chapter 1.4.5.2 --- The Type 1 Angiotensin Receptor Gene --- p.36 / Chapter 1.4.6 --- Dopamine --- p.39 / Chapter 1.4.6.1 --- Dopamine Receptors --- p.42 / Chapter 1.4.6.2 --- The Dopamine D2 Receptor Gene --- p.45 / Chapter 2 --- Aims --- p.47 / Chapter 3 --- Materials and methodology --- p.48 / Chapter 3.1 --- Patient recruitment protocol --- p.48 / Chapter 3.2 --- Subjects --- p.49 / Chapter 3.2.1 --- Classification of Hypertension --- p.50 / Chapter 3.2.2 --- Definition of Dyslipidaemia --- p.51 / Chapter 3.2.3 --- Classification of Diabetes Mellitus --- p.52 / Chapter 3.2.4 --- Definition of Obesity --- p.53 / Chapter 3.2.5 --- Exclusion Criteria --- p.54 / Chapter 3.3 --- Routine Assessment --- p.54 / Chapter 3.3.1 --- Blood Pressure --- p.54 / Chapter 3.3.2 --- Measurements of obesity --- p.55 / Chapter 3.3.2.1 --- Body mass index --- p.55 / Chapter 3.3.2.2 --- Waist to hip ratio --- p.55 / Chapter 3.3.2.3 --- Skin-Fold Thickness --- p.55 / Chapter 3.3.2.4 --- Skinfold Percentage Fat --- p.56 / Chapter 3.3.3 --- Biochemical measurements --- p.56 / Chapter 3.3.3.1 --- Assays measuring biochemical factors from plasma --- p.57 / Chapter 3.3.3.1.1 --- Plasma electrolytes --- p.57 / Chapter 3.3.3.1.2 --- Plasma urate --- p.57 / Chapter 3.3.3.1.3 --- Plasma creatinine --- p.57 / Chapter 3.3.3.1.4 --- Fasting plasma glucose --- p.57 / Chapter 3.3.3.1.5 --- Fasting plasma cholesterol --- p.57 / Chapter 3.3.3.1.6 --- Fasting plasma triglyceride --- p.58 / Chapter 3.3.3.2 --- Assays measuring biochemical factors from urine --- p.58 / Chapter 3.3.3.2.1 --- Urinary electrolytes --- p.58 / Chapter 3.3.3.2.2 --- Urinary creatinine --- p.58 / Chapter 3.3.3.2.3 --- Urinary albumin concentration --- p.58 / Chapter 3.4 --- Extraction of DNA from blood specimen --- p.59 / Chapter 3.5 --- Polymerase Chain Amplification protocols --- p.60 / Chapter 3.5.1 --- Uncoupling protein 1 gene polymorphism --- p.60 / Chapter 3.5.2 --- Angiotensin-Converting Enzyme insertion-deletion polymorphism --- p.62 / Chapter 3.5.3 --- Angiotensin type 1 receptor gene A1166C polymorphism --- p.64 / Chapter 3.5.4 --- Dopamine D2 receptor TaqI polymorphism --- p.66 / Chapter 3.5.5 --- Dopamine D2 receptor TaqI polymorphism --- p.66 / Chapter 3.6 --- Statistical analysis --- p.68 / Chapter 3.6.1 --- Paired sample T test --- p.68 / Chapter 3.6.2 --- Conditional Logistic Regression --- p.68 / Chapter 3.6.3 --- Linkage analysis --- p.69 / Chapter 3.6.3.1 --- Allelic frequency and genotypic distribution --- p.69 / Chapter 3.6.3.2 --- Hardy- Weinberg equilibrium --- p.69 / Chapter 3.6.3.3 --- Parametric analysis --- p.71 / Chapter 3.6.3.4 --- Nonparametric analysis --- p.71 / Chapter 3.6.3.4.1 --- The affected sib pair (ASP) method --- p.74 / Chapter 3.6.3.4.2 --- The affected pedigree member (APM) method of linkage analysis --- p.76 / Chapter 3.6.3.4.3 --- Quantitative traits linkage analysis --- p.79 / Chapter 4 --- Results --- p.81 / Chapter 4.1 --- Description of the characteristics of in siblings --- p.81 / Chapter 4.1.1 --- Siblings and sib-pairs --- p.81 / Chapter 4.1.2 --- Demographic characteristics --- p.81 / Chapter 4.1.3 --- Relationship to age and gender --- p.83 / Chapter 4.1.3.1 --- Hypertension versus age and gender --- p.83 / Chapter 4.1.3.2 --- Central obesity versus age and gender --- p.83 / Chapter 4.1.3.3 --- General obesity versus age and gender --- p.84 / Chapter 4.1.3.4 --- Hypertension-central obesity versus age and gender --- p.84 / Chapter 4.1.3.5 --- Hypertension- general obesity versus age and gender --- p.85 / Chapter 4.1.4 --- Relationship to anthropometric indices --- p.85 / Chapter 4.1.4.1 --- Large proportion of obesity --- p.85 / Chapter 4.1.4.2 --- Hypertension versus anthropometric indices --- p.86 / Chapter 4.1.5 --- Relationship to biochemistry indices --- p.87 / Chapter 4.1.5.1 --- Large proportion of dyslipidaemia --- p.87 / Chapter 4.2 --- Association between disease traits and covariates in discordant sib pairs --- p.87 / Chapter 4.2.1 --- Association between blood pressure and covariates in discordant sib-pairs --- p.87 / Chapter 4.2.2 --- Association between general obesity and covariates in discordant sib-pairs --- p.89 / Chapter 4.2.3 --- Association between obesity related hypertension and covariates in combined discordant sib-pairs --- p.91 / Chapter 4.3 --- Description of the analysis of the polymorphisms of 4 genes which might be related to hypertension and obesity --- p.93 / Chapter 4.3.1 --- The uncoupling protein 1 gene --- p.93 / Chapter 4.3.1.1 --- Comparison of A-G polymorphism in terms of hypertension or obesity --- p.94 / Chapter 4.3.1.2 --- Comparison of A-G polymorphism in terms of HT and obesity --- p.97 / Chapter 4.3.1.3 --- Comparison of characteristics among different genotypes --- p.99 / Chapter 4.3.2 --- The angiotensin-converting enzyme gene --- p.99 / Chapter 4.3.2.1 --- Comparison of the ACE I/D polymorphism in terms of HT --- p.100 / Chapter 4.3.2.2 --- Comparison of characteristics among different genotypes --- p.101 / Chapter 4.3.3 --- The angiotensin type 1 receptor gene --- p.104 / Chapter 4.3.3.1 --- Comparison of the A T1R A1166C polymorphism in terms of HT --- p.104 / Chapter 4.3.3.2 --- Comparison of characteristics among different genotypes --- p.105 / Chapter 4.3.4 --- The Dopamine D2 receptor gene --- p.105 / Chapter 4.3.4.1 --- Comparison of the DRD2 gene TaqI polymorphism in terms of HT --- p.106 / Chapter 4.3.4.2 --- Comparison of the DRD2 gene TaqI polymorphism in terms of general obesity or central obesity --- p.108 / Chapter 4.3.4.3 --- Comparison of the DRD2 gene TaqI polymorphism in terms of general obesity/central obesity and HT --- p.110 / Chapter 4.4 --- Sib pair linkage analysis --- p.113 / Chapter 4.4.1 --- Linkage between each gene and hypertension in our data --- p.114 / Chapter 4.4.1.1 --- Genetic linkage of the marker near the UCP1 gene locus to hypertension --- p.114 / Chapter 4.4.1.2 --- Genetic linkage of the angiotens in-converting enzyme gene locus to hypertension --- p.116 / Chapter 4.4.1.3 --- Genetic linkage of the angiotensin type 1 (AT1) receptor gene locus to hypertension --- p.117 / Chapter 4.4.1.4 --- Genetic linkage of the dopamine D2 receptor gene locus to hypertension --- p.118 / Chapter 4.4.2 --- Linkage between each gene locus and obesity in Hong Kong hypertensive Chinese families --- p.120 / Chapter 4.4.2.1 --- Genetic linkage of the uncoupling protein 1 gene locus to obesity with hypertensive family history --- p.120 / Chapter 4.4.2.2 --- Genetic linkage of the angiotens in-converting enzyme gene locus to obesity with hypertensive family history --- p.123 / Chapter 4.4.2.3 --- Genetic linkage of the angiotensin type 1 receptor gene locus to obesity with hypertensive family history --- p.124 / Chapter 4.4.2.4 --- Genetic linkage of the dopamine D2 gene locus to obesity --- p.127 / Chapter 5 --- Discussion --- p.129 / Chapter 5.1 --- Age-related anomalies --- p.129 / Chapter 5.2 --- Gender-related anomalies --- p.129 / Chapter 5.3 --- Obesity- related hypertension --- p.130 / Chapter 5.4 --- Abnormal biochemical parameters in hypertension --- p.131 / Chapter 5.5 --- Genetic parameters involved in the pathogenesis of hypertension and obesity. --- p.132 / Chapter 5.6 --- The uncoupling protein gene --- p.132 / Chapter 5.6.1 --- Higher frequency in central obese males --- p.132 / Chapter 5.6.2 --- Linkage of systolic blood pressure with G allele --- p.134 / Chapter 5.6.3 --- Metabolic link --- p.135 / Chapter 5.7 --- The angiotensin-converting enzyme gene --- p.137 / Chapter 5.7.1 --- The ACE D allele and hypertension in previous studies --- p.137 / Chapter 5.7.2 --- Positive role of the ACE DD genotype found in our data --- p.139 / Chapter 5.8 --- Angiotensin II type 1 receptor gene --- p.141 / Chapter 5.8.1 --- No linkage with HT --- p.141 / Chapter 5.9 --- Dopamine D2 gene --- p.143 / Chapter 5.9.1 --- Dopamine and obesity --- p.143 / Chapter 5.9.2 --- Linkage with obese and HT --- p.144 / Chapter 5.10 --- Summary of the study --- p.146 / Chapter 5.11 --- Possible further developments in this study --- p.146 / Chapter 6 --- References --- p.148

Although essential hypertension has long been recognized to involve a strong genetic predisposition, the genes that increase susceptibility remain virtually unknown. With recent advances in molecular biology and statistical methods, it has become feasible to study candidate genes which may contribute to the pathogenesis of essential hypertension in humans. We identified the polymorphisms of five genes by applying a micoarray genotyping system for multiplex analysis of a panel of single nucleotide polymorphisms (SNPs) in genes involved in the regulation of blood pressure, then determined whether specific SNPs in genes were related to blood pressure in Hong Kong Chinese. / Based on the study results, we conclude that blood pressure levels are determined by complex interactions between genetic and environmental factors. The AGT gene 235T and the DD1R gene -48G alleles strongly predicted the development of hypertension in Hong Kong Chinese. The variants of the DD2R gene and the UCP1 gene A-3826G variant only weakly impacted upon blood regulation. However, the three variants of the INSR gene and the L10F variant of the AGT gene were not detected in Hong Kong Chinese. Although success in identifying single genes contributing to hypertension has been limited, the use of intermediate phenotypes and dense mapping of candidate genes shows the influence of gene-gene interaction on hypertension or obesity-related hypertension in our hypertensive families of Hong Kong Chinese. / Families were recruited if the proband was found to have hypertension and had siblings resident in Hong Kong. We identified 126 families with at least one hypertensive sibling. A total of 434 siblings were studied. All subjects underwent clinical and biochemical investigation to exclude those with either secondary hypertension, impaired glucose tolerance or type 2 diabetes mellitus. / Twelve SNPs in five candidate genes, which included the M235T, T174M, G-217A and L10F polymorphisms of the angiotensinogen gene (AGT); A-48G polymorphism of the dopamine D1 receptor gene (DD1R); the TaqI A, -141C Ins/Del and A-241G polymorphisms of the dopamine D2 receptor gene (DD2R); Phe382Val, Lys460Glu, and Gly1008Val polymorphisms of the insulin receptor gene (INSR); and the A-3826G polymorphism of the uncoupling protein 1 gene (UCP1). / by Fang Yujing. / "January 2006." / Adviser: Brian Tomlinson. / Source: Dissertation Abstracts International, Volume: 67-11, Section: B, page: 6298. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 148-181). / 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.

BACKGROUND: Clinical evidence shows that diabetes may provoke uncontrolled blood pressure (BP) in hypertensive patients. However, racial differences in the associations of diabetes with uncontrolled BP outcomes among diagnosed hypertensive patients have not been evaluated. METHODS: A total of 6,134 diagnosed hypertensive subjects aged ≥ 20 years were collected from the National Health and Nutrition Examination Survey 1999-2008 with a stratified multistage design. Odds ratios (ORs) and relative ORs of uncontrolled BP and effect differences in continuous BP for diabetes over race/ethnicity were derived using weighted logistic regression and linear regression models. RESULTS: Compared with participants who did not have diabetes, non-Hispanic black participants with diabetes had a 138% higher chance of having uncontrolled BP, Mexican participants with diabetes had a 60% higher chance of having uncontrolled BP, and non-Hispanic white participants with diabetes had a 161% higher chances of having uncontrolled BP. The association of diabetes with uncontrolled BP was lower in Mexican Americans than in non-Hispanic blacks and whites (Mexican Americans vs. non-Hispanic blacks: relative OR = 0.55, 95% confidence interval (CI) = 0.37-0.82; Mexican Americans vs. non-Hispanic whites: relative OR = 0.53, 95% CI = 0.35-0.80) and the association of diabetes with isolated uncontrolled systolic BP was lower in Mexican Americans than in non-Hispanic whites (Mexican Americans vs. non-Hispanic whites: relative OR = 0.62, 95% CI = 0.40-0.96). Mexican Americans have a stronger association of diabetes with decreased systolic BP and diastolic BP than non-Hispanic whites, and a stronger association of diabetes with decreased diastolic BP than non-Hispanic blacks. CONCLUSIONS: The association of diabetes with uncontrolled BP outcomes is lower despite higher prevalence of diabetes in Mexican Americans than in non-Hispanic whites. The stronger association of diabetes with BP outcomes in whites should be of clinical concern, considering they account for the majority of the hypertensive population in the United States.