Liu, Zhi Kai. / Thesis submitted in: December 2006. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 105-117). / Abstracts in English and Chinese. / Abstract (English version) --- p.i / Abstract (Chinese version) --- p.v / Acknowledgement --- p.vii / Statement of contribution --- p.x / Table of Contents --- p.xi / List of Tables --- p.xv / List of Figures --- p.xviii / List of Abbreviations --- p.xix / Publications arising from this thesis --- p.xxi / Chapter Chapter One --- Introduction / Chapter 1.1 --- "Lipids, lipoproteins and lipid metabolism" --- p.1 / Chapter 1.1.1 --- Cholesterol --- p.1 / Chapter 1.1.2 --- Triglycerides --- p.2 / Chapter 1.1.3 --- Lipoproteins and their metabolic pathways --- p.3 / Chapter 1.2 --- Familial combined hyerlipidemia and combined hyperlipidemia --- p.4 / Chapter 1.3 --- Single nucleotide polymorphisms --- p.9 / Chapter 1.3.1 --- SNP genotyping methods --- p.9 / Chapter 1.3.2 --- Association of SNPs with genetic diseases --- p.10 / Chapter 1.4 --- Genetic analysis of FCH and CH --- p.10 / Chapter 1.4.1 --- FCH genome scans --- p.11 / Chapter 1.4.2 --- SNP based candidate gene analysis --- p.11 / Chapter 1.5 --- Candidate genes and SNPs associated with FCH and CH --- p.12 / Chapter 1.5.1 --- Apolipoprotein A1/C3/A4/A5 gene cluster --- p.12 / Chapter 1.5.1.1 --- Apolipoprotein A1 gene --- p.15 / Chapter 1.5.1.2 --- Apolipoprotein C3 gene --- p.16 / Chapter ].5.1.3 --- Apolipoprotein A4 gene --- p.17 / Chapter 1.5.1.4 --- Apolipoprotein A5 gene --- p.18 / Chapter 1.5.2 --- Upstream transcription factor 1 gene --- p.24 / Chapter 1.5.3 --- Lipoprotein lipase gene --- p.25 / Chapter 1.5.4 --- Peroxisome proliferators-activated receptor γ gene --- p.26 / Chapter 1.5.5 --- a-adducin gene --- p.27 / Chapter 1.5.6 --- SNPs selected from the haplotype map --- p.27 / Chapter 1.6 --- Objectives --- p.28 / Chapter Chapter Two --- Materials and methods / Chapter 2.1 --- Overview --- p.31 / Chapter 2.2 --- Routine assessments --- p.32 / Chapter 2.2.1 --- Genetic hyperlipidemia survey --- p.32 / Chapter 2.2.2 --- Physical examinations --- p.33 / Chapter 2.2.3 --- Biochemical measurements --- p.33 / Chapter 2.2.3.1 --- Fasting plasma cholesterol --- p.33 / Chapter 2.2.3.2 --- Fasting plasma triglyceride --- p.34 / Chapter 2.2.3.3 --- Fasting plasma glucose --- p.34 / Chapter 2.3 --- Subjects --- p.34 / Chapter 2.3.1 --- FCH cases --- p.34 / Chapter 2.3.2 --- CH cases --- p.35 / Chapter 2.3.3 --- Normal controls --- p.36 / Chapter 2.4 --- DNA extraction from blood specimens --- p.36 / Chapter 2.4.1 --- Phenol chloroform method --- p.36 / Chapter 2.4.2 --- High pure PCR template preparation kit (Roche) --- p.37 / Chapter 2.5 --- Genotyping by the MassARRAY system --- p.38 / Chapter 2.6 --- Statistical analyses --- p.40 / Chapter 2.6.1 --- Overview --- p.40 / Chapter 2.6.2 --- Student's t-test --- p.41 / Chapter 2.6.3 --- Pearson's Chi-square test --- p.41 / Chapter 2.6.4 --- Hardy-Weinberg equilibrium --- p.41 / Chapter 2.6.5 --- Binary logistic regression test --- p.42 / Chapter 2.6.6 --- Analysis of covariance --- p.43 / Chapter 2.6.7 --- Haplotype analysis --- p.43 / Chapter 2.6.8 --- Bonferroni's correction --- p.44 / Chapter Chapter Three --- Results / Chapter 3.1 --- Overview --- p.46 / Chapter 3.2 --- Characteristics of the study population --- p.47 / Chapter 3.2.1 --- FCH cases versus controls --- p.47 / Chapter 3.2.2 --- CH cases versus controls --- p.50 / Chapter 3.3 --- Hardy-Weinberg equilibrium --- p.52 / Chapter 3.3.1 --- FCH cases and controls --- p.52 / Chapter 3.3.2 --- CH cases and controls --- p.53 / Chapter 3.4 --- APOA1/C3/A4/A5 gene cluster --- p.56 / Chapter 3.4.1 --- FCH cases versus controls --- p.56 / Chapter 3.4.1.1 --- Genotypic distribution and allelic frequency --- p.56 / Chapter 3.4.1.2 --- Odds ratio --- p.59 / Chapter 3.4.1.3 --- Parameter analysis --- p.61 / Chapter 3.4.1.4 --- Haplotype analysis --- p.68 / Chapter 3.4.2 --- CH cases versus controls --- p.69 / Chapter 3.4.2.1 --- Genotypic distribution and allelic frequency --- p.69 / Chapter 3.4.2.2 --- Odds ratio --- p.70 / Chapter 3.4.2.3 --- Parameter analysis --- p.74 / Chapter 3.4.2.4 --- Haplotype analysis --- p.83 / Chapter 3.5 --- USF1 gene --- p.84 / Chapter 3.5.1 --- FCH cases versus controls --- p.84 / Chapter 3.5.2 --- CH cases versus controls --- p.85 / Chapter 3.6 --- LPL gene --- p.87 / Chapter 3.6.1 --- FCH cases versus controls --- p.87 / Chapter 3.6.2 --- CH cases versus controls --- p.88 / Chapter 3.7 --- PPARγgene --- p.89 / Chapter 3.7.1 --- FCH cases versus controls --- p.89 / Chapter 3.7.2 --- CH cases versus controls --- p.90 / Chapter 3.8 --- ADD] gene --- p.91 / Chapter 3.8.1 --- FCH cases versus controls --- p.91 / Chapter 3.8.2 --- CH cases versus controls --- p.91 / Chapter Chapter Four --- Discussion / Chapter 4.1 --- Comparisons of the findings with these of other studies --- p.93 / Chapter 4.1.1 --- APOA1/C3/A4/A5 gene cluster --- p.93 / Chapter 4.1.1.1 --- APOA1 --- p.93 / Chapter 4.1.1.2 --- APOC3 --- p.94 / Chapter 4.1.1.3 --- APOA4 --- p.96 / Chapter 4.1.1.4 --- APOA4-A5 --- p.96 / Chapter 4.1.1.5 --- APOA5 --- p.97 / Chapter 4.1.2 --- USF1 --- p.101 / Chapter 4.1.3 --- LPL --- p.102 / Chapter 4.1.4 --- PPARγ --- p.102 / Chapter 4.1.5 --- ADD1 --- p.03 / Chapter 4.2 --- Conclusions --- p.103 / Chapter 4.3 --- Implications for future research --- p.104 / References --- p.105