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Association study of transcription factors regulating insulin secretion and action in type 2 diabetes in Chinese.

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

Identiferoai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_326447
Date January 2008
ContributorsHo, Sin Ka Janice., Chinese University of Hong Kong Graduate School. Division of Medical Sciences.
Source SetsThe Chinese University of Hong Kong
LanguageEnglish, Chinese
Detected LanguageEnglish
TypeText, bibliography
Formatprint, xv, 155 leaves : col. ill., col. maps ; 30 cm.
RightsUse 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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