Ho Sin Ka Janice. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 105-119). / Abstracts in English and Chinese. / Chapter CHAPTER 1. --- Introduction / Chapter 1.1. --- Epidemiology of Type 2 Diabetes --- p.1 / Chapter 1.2. --- Risk factors contributing to Type 2 Diabetes --- p.3 / Chapter 1.2.1. --- Environmental and physiological factors --- p.3 / Chapter 1.2.2. --- Genetic factors --- p.3 / Chapter 1.3. --- Disruption of energy homeostasis in the pathogenesis of type 2 diabetes --- p.6 / Chapter 1.3.1. --- Clinical spectrum of diabetes --- p.6 / Chapter 1.3.2. --- Insulin as a key regulator of energy homeostasis --- p.7 / Chapter 1.3.3. --- Insulin secretion and glucose metabolism --- p.8 / Chapter 1.3.4. --- Insulin action and lipid metabolism --- p.9 / Chapter 1.3.5. --- Lipotoxicity and glucotoxicity --- p.12 / Chapter 1.3.6. --- Role of transcription factors as metabolic switch --- p.13 / Chapter 1.4. --- Candidate genes implicated in type 2 diabetes susceptibility --- p.15 / Chapter 1.4.1. --- Candidate genes involved in insulin secretion pathway --- p.15 / Chapter 1.4.1.1. --- HNF4A --- p.15 / Chapter 1.4.1.2. --- HNF1A --- p.16 / Chapter 1.4.1.3. --- PDX1/PBX1 --- p.17 / Chapter 1.4.1.4. --- NEUROD1 --- p.17 / Chapter 1.4.1.5. --- GCK --- p.17 / Chapter 1.4.1.6. --- KCNJ11/ABCC8 --- p.18 / Chapter 1.4.2 --- Candidate genes involved in insulin action pathway --- p.19 / Chapter 1.4.2.1. --- PPARG --- p.19 / Chapter 1.4.2.2. --- PPARA --- p.20 / Chapter 1.4.2.3. --- PPARGC1A --- p.20 / Chapter 1.4.2.4. --- ADIP0Q --- p.21 / Chapter 1.4.2.5. --- LPL --- p.21 / Chapter 1.4.2.6. --- UPC --- p.22 / Chapter 1.5. --- Hypothesis and objectives of the study --- p.23 / Chapter CHAPTER 2. --- Materials and methods / Chapter 2.1. --- Study design --- p.25 / Chapter 2.1.1. --- Two-stage candidate gene association design --- p.25 / Chapter 2.1.2. --- Power calculation --- p.27 / Chapter 2.2. --- Study cohort --- p.29 / Chapter 2.2.1. --- Subject recruitment --- p.29 / Chapter 2.2.2. --- Clinical and biochemical measurements --- p.30 / Chapter 2.2.3. --- Clinical definitions --- p.31 / Chapter 2.3. --- Genetic study --- p.32 / Chapter 2.3.1. --- Candidate gene selection --- p.32 / Chapter 2.3.2. --- SNP selection --- p.32 / Chapter 2.3.3. --- DNA sample preparation --- p.35 / Chapter 2.3.4. --- Genotyping methods --- p.36 / Chapter 2.3.4.1. --- Allele specific Tm shift assay --- p.36 / Chapter 2.3.4.2. --- Mass spectrometry assay --- p.40 / Chapter 2.4. --- Data quality control --- p.42 / Chapter 2.4.1. --- Stage 1 --- p.42 / Chapter 2.4.2. --- Stage 2 --- p.42 / Chapter 2.5. --- Statistical analysis --- p.45 / Chapter 2.5.1. --- Stage 1 analysis --- p.45 / Chapter 2.5.2. --- Stage 2 analysis --- p.45 / Chapter 2.5.3. --- Stage 1 and 2 combined analysis --- p.46 / Chapter CHAPTER 3. --- Results / Chapter 3.1. --- Clinical characteristics of subjects in stages 1 and 2 studies --- p.48 / Chapter 3.2. --- Case-control associations in stage 1 --- p.51 / Chapter 3.2.1. --- Association with T2D --- p.51 / Chapter 3.2.2. --- Association with T2D subset by metabolic syndrome --- p.54 / Chapter 3.3. --- Case-control associations in stage 2 --- p.60 / Chapter 3.3.1. --- SNP selection for genotyping --- p.60 / Chapter 3.3.2. --- Association with T2D --- p.63 / Chapter 3.3.3. --- Association with T2D subset by metabolic syndrome --- p.64 / Chapter 3.4. --- Case-control associations in combined stages 1 and 2 --- p.66 / Chapter 3.4.1. --- Association with T2D --- p.66 / Chapter 3.4.2. --- Association with T2D subset by metabolic syndrome --- p.70 / Chapter 3.4.3. --- Association with T2D subset by age at diagnosis --- p.74 / Chapter 3.4.4. --- Association with T2D subset by gender --- p.76 / Chapter 3.4.5. --- Genetic epistasis for T2D association --- p.79 / Chapter 3.5. --- Metabolic traits associations in control subjects in combined stages 1 and 2 studies --- p.83 / Chapter CHAPTER 4. --- Discussion --- p.86 / Chapter 4.1. --- Role of insulin secretion genes in type 2 diabetes --- p.87 / Chapter 4.2. --- Role of insulin action genes in type 2 diabetes --- p.92 / Chapter 4.3. --- Combined genetic effects on risk for type 2 diabetes --- p.97 / Chapter 4.4. --- Summary --- p.98 / Chapter 4.5. --- Limitation of this study and future direction --- p.101 / REFERENCES --- p.104 / APPENDICES --- p.119 / Chapter Appendix 1: --- Gene structure and linkage disequilibrium of genotyped SNPs of candidate genes --- p.119 / Chapter Appendix 2: --- Information of SNPs genotyped in stage 1 --- p.130 / Chapter Appendix 3: --- T2D association results (additive model) of 152 SNPs for stage 1 case- control samples --- p.137 / Chapter Appendix 4: --- T2D association results (additive model) of 152 SNPs for stage 1 case- control samples subset by metabolic syndrome status in cases --- p.144 / Chapter Appendix 5: --- T2D association results (additive model) of 22 SNPs for stage 2 case- control samples --- p.151 / Chapter Appendix 6: --- T2D association results (additive model) of 22 SNPs for stage 2 case- control samples subset by metabolic syndrome status in cases --- p.153
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_326447 |
| Date | January 2008 |
| Contributors | Ho, Sin Ka Janice., Chinese University of Hong Kong Graduate School. Division of Medical Sciences. |
| Source Sets | The Chinese University of Hong Kong |
| Language | English, Chinese |
| Detected Language | English |
| Type | Text, bibliography |
| Format | print, xv, 155 leaves : col. ill., col. maps ; 30 cm. |
| Rights | Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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