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系統識別號 U0026-1807201023355400
論文名稱(中文) 過氧化體增殖劑活化受器PPARδ單核苷酸基因多型性與心肌梗塞及梗塞嚴重度及代謝發炎指標之相關性分析
論文名稱(英文) Association analysis of SNPs in PPARδ gene with myocardial infarction,infarct severity and metabolic-inflammatory markers
校院名稱 成功大學
系所名稱(中) 臨床醫學研究所
系所名稱(英) Institute of Clinical Medicine
學年度 98
學期 2
出版年 99
研究生(中文) 蔣俊彥
研究生(英文) Chun-Yen Chiang
學號 s9796116
學位類別 碩士
語文別 英文
論文頁數 98頁
口試委員 指導教授-蔡曜聲
召集委員-李貽恆
口試委員-郭柏秀
口試委員-曾慶誠
中文關鍵字 單核苷酸基因多型性  過氧化體增殖劑活化受器PPARδ  心肌梗塞  梗塞嚴重度  身體質量比  高敏感性C-反應蛋白 
英文關鍵字 single nucleotide polymorphisms  peroxisome proliferators-activated receptor delta  myocardial infarction  infarct severity  body mass index  high-sensitivity C-reactive protein 
學科別分類
中文摘要 過氧化體增殖劑活化受器PPARδ是種鍵結形式活化的轉錄因子,作用在脂質和葡萄糖的代謝。有證據顯示PPARδ基因的活化減少發炎和動脈硬化。然而過氧化體增殖劑活化受器PPARδ基因多型性和心肌梗塞之相關性不清楚。我們假設PPARδ單核苷酸基因多型性和心肌梗塞的發生有相關性,並且其基因型多型性影響心肌梗塞嚴重度相關。另外我們也希望藉此分析過氧化體增殖劑活化受器PPARδ基因多型性和已知心肌梗塞相關之發炎及代謝指標之相關性。
我們設計一個病例對照組實驗,心肌梗塞病患為實驗組共有154人, 無心血管阻塞及心肌梗塞病患為對照組共有149人。我們選擇三個PPARδ基因的位點rs2016520, rs2267668 和 rs1053049做分析,並記錄所有受試者的膽固醇值、血糖值、心肌酵素、身體質量比及高敏感性C-反應蛋白。
我們利用多項式邏輯迴歸分析探討基因相關性及多元線性迴歸做特徵量化分析。結果顯示三個PPARδ基因的位點rs2016520,rs2267668 和rs1053049其單核苷酸基因多型性和心肌梗塞並無相關,且也和心肌梗塞嚴重度沒有相關,但把所有受試者做相關性分析,顯示過氧化體增殖劑活化受器PPARδ基因多型性和身體質量比及糖尿病有相關,且在心肌梗塞病患其高敏感性C-反應蛋白(hs-CRP)和PPARδ單核苷酸基因多型性有相關性。在特徵量性分析方面,在所有受試者過氧化體增殖劑活化受器PPARδ基因多型性和身體質量比及高密度脂蛋白(HDL)有相關性;另外在心肌梗塞患者過氧化體增殖劑活化受器PPARδ基因多型性和高敏感性C-反應蛋白及白血球數量有關。
從我們的結果顯示PPARδ單核苷酸基因多型性和心肌梗塞及梗塞嚴重度無關,但和身體質量比及糖尿病有相關,且在心肌梗塞的病患PPARδ單核苷酸基因多型性和高敏感性C-反應蛋白有相關性。
英文摘要 Peroxisome proliferators-activated receptor delta (PPARδ) is a ligand-activated transcriptional factor involved in lipid and glucose metabolism. Evidences showed PPAR δ gene activation limit inflammation and atherosclerosis. The association of the genetic variants of PPARδ and myocardial infarction (MI) remain unclear. We hypothesized that genetic variants of PPARδ gene is associated with myocardial infarction and the severity of myocardial infarction. Secondly, we also wanted to study the association of the genetic variants of PPARδ gene with inflammatory and metabolic markers, which are known to be related to MI.
We designed a case-control study and finally recruited 154 patients with MI as case-group and 149 patients without MI and coronary artery stenosis as control-group from July 2008 to October 2009 in Chi-Mei medical center. We chose three loci of PPARδ including rs2016520, rs2267668 and rs1053049. Lipid profiles, glucose, cardiac enzymes, body mass index (BMI) and high-sensitivity C-reactive protein (hs-CRP) were recorded in all subjects.
In our results, genetic association test were carried out using multivariate logistic regression. Multivariate linear regression was used in quantitative analysis of metabolic-inflammatory traits. We found that the genetic variants of PPARδ were not associated with myocardial infarction and infarct severity. However, BMI and diabetes mellitus were associated with the genetic variants of rs2016520, rs2267668 and rs1053049 in all subjects. In quantitative traits analysis, the genetic variants of PPARδ have significant association in BMI and high-density lipoprotein (HDL) in all subjects. In addition, hs-CRP and white blood counts were associated with genetic variants of PPARδ in MI group.
In conclusion, while genetic variants of PPARδ are not associated with myocardial infarction and infarct size, they are associated with BMI in all subjects, and the level of hs-CRP in MI group.
論文目次 Thesis Contents
Chinese abstract..........................................3
Abstract..................................................5
Acknowledge...............................................7
Thesis contents...........................................8
Abbreviations............................................14
Chapter 1 Introduction...................................17
1.1 Background.......................................17
1.2 Review of literature.............................18
1.2.1 Candidate genetic variants and coronary artery disease..................................................18
1.2.2 PPAR............................................ 20
1.2.3 PPAR agonists....................................24
1.2.4 General mechanism of PPARδ.......................26
1.2.4.1 Effects on metabolism............................26
1.2.4.2 Effects on inflammation..........................29
1.2.4.3 Effects on atherosclerosis.......................31
1.2.5 Clinical research for genetic variants in PPARδ..32
1.2.6 SNPs locations in PPARδ..........................36
1.3 Aims of the study....................................36
Chapter 2 Methods........................................38
2.1 Study population.....................................38
2.1.1 Case group.........................................38
2.1.2 Controlled group...................................38
2.1.3 Study protocol.....................................39
2.1.4 Inform consent.....................................39
2.1.5 Sample size calculation............................39
2.2 Data collection......................................39
2.2.1 Clinical parameters................................39
2.2.2 Biomarker analysis.................................40
2.2.3 History review.....................................40
2.2.4 Diagnosis of myocardial infarction and myocardial infarct size evaluation..................................41
2.3 Blood collection and DNA analysis....................42
2.3.1 DNA extraction.....................................42
2.3.2 Genotyping and SNP analysis........................43
2.3.3 Selection of SNPs..................................44
2.4 Statistical analyses.................................44
2.5 Subjects recruitment.................................45
Chapter 3 Results........................................47
3.1 Association analysis of genetic variants in PPARδ with myocardial infarction and infarct severity...............47
3.2 Association analysis of metabolic and inflammatory markers..................................................48
3.2.1 Association analysis of genetic variants in PPARδ and BMI..................................................48
3.2.2 Association analysis of genetic variants in PPARδ and hs-CRP...............................................49
3.2.3Association analysis of genetic variants in PPARδ and cholesterol..............................................50
3.3 Quantitative analysis of metabolic and inflammatory markers..................................................50
3.3.1 Quantitative analysis of genetic variants in PPARδ and BMI..................................................50
3.3.2 Quantitative analysis of genetic variants in PPARδ and hs-CRP...............................................51
3.3.3 Quantitative analysis of genetic variants in PPARδ and cholesterol..........................................51
3.4 Linkage disequilibrium and Hardy-Weinberg equilibrium in PPARδ.................................................51
3.5 Association analysis of genetic variants in PPARδ and diabetes.................................................52
Chapter 4 Discussion.....................................53
Limitation and difficulties in the study.................60
Conclusion...............................................61
Flow chart of the study..................................62
Tables...................................................63
Figures..................................................69
References...............................................75
Supplement data..........................................87
Curriculum Vitae.........................................96
Appendix.................................................98

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