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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳為堅 | |
dc.contributor.author | Ya-Tang Liao | en |
dc.contributor.author | 廖雅堂 | zh_TW |
dc.date.accessioned | 2021-06-15T06:55:36Z | - |
dc.date.available | 2012-02-01 | |
dc.date.copyright | 2011-03-03 | |
dc.date.issued | 2011 | |
dc.date.submitted | 2011-02-09 | |
dc.identifier.citation | 1. Kapaj S, Peterson H, Liber K, Bhattacharya P. Human health effects from chronic arsenic poisoning--a review. J Environ Sci Health A Tox Hazard Subst Environ Eng 2006;41:2399-428.
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/48407 | - |
dc.description.abstract | 心臟及血管疾病為世界各地主要的致死原因之一,危險因子相對風險之些微的提升即會造成很顯著的死亡人口的增加。砷是已明確證明主要與心血管疾病以及惡性腫瘤有關但是可經由後天修飾的一種環境污染物質。砷所造成的心血管疾病可能由遺傳因子與環境因子的毒性機制所共同作用的結果,然而對於心血管疾病死亡率提高多少是歸因於遺傳因子所造成目前仍無充分資料。目前已有許多已發表慢性砷暴露與心血管疾病之關連性研究,但大部份僅限於橫斷型的研究設計而較缺乏長期追蹤的科學證據。此外,絕大部份研究專注在探討砷所引起之臨床心血管疾病,而較少研究討論疾病發展之前期或早期的臨床表現。因此,使用這些前期及早期臨床表徵來評估砷所造成的慢性中毒有其重要性。本研究之主要目的即欲探討巴拉松酶(Paraoxonase, PON1)、三價砷甲基化酶(AS3MT)以及榖胱苷肽硫轉移酶(GSTO1)等基因以及慢性砷暴露作用於乳酸去氫酶(Lactate dehydrogenase, LDH)以及心電圖異常等臨床前期表現之加成效應,並檢驗砷代謝能力是否會調節砷所造成的心血管疾病風險。根據我們的結果顯示,即使在停止慢性砷暴露數十年之後,心血管疾病之臨床前期指標仍與暴露量存在某種程度的關連,顯示砷之長期的健康危害。而在停止暴露若干年之後,尿中砷代謝之物種更能反應長期砷暴露之指標。此外,本研究發現顯著作用於臨床前期之基因與基因,基因與環境交互作用。這些結果可以提供目前砷暴露地區之飲用水風險管控提供重要的參考。 | zh_TW |
dc.description.abstract | Cardiovascular disease is a major cause of mortality worldwide, small increase in odds ratio may result in significant excess number of deaths. Arsenic is a potent but modifiable environmental pollutant that has been linked to increased prevalence of cardiovascular disease (CVD) and cancer globally. Arsenic-induced CVD may result from the inter-correlations among genetic, environmental factors though toxicological mechanisms. However much less was known about the excess mortality from arsenic with genetic factors considered. Although an association between chronic arsenic exposure and CVD has been found in many studies, nearly all of these studies were limited by use of cross-sectional data, and longitudinal evidence by follow-up study was still limited. Besides, majority of previous studies were focus on the clinical arsenic-related cardiovascular disease, instead of the manifest of preclinical or subclinical detections. Studies based on subclinical finding are needed to detect the early sign of chronic poisoning. The objective of this study is to investigate the joint contribution of genetic factors including PON1, AS3MT, and GSTO gene families and the long-term arsenic impacts on cardiovascular disease through measuring plasma LDH levels and ECG abnormality as subclinical phenotypes and to evaluate whether the arsenic methylation patterns modifies the association between cumulative arsenic exposure and the risk of CVD. Our studies demonstrated after cessation of arsenic-contaminated water consumption for decades, biomarkers for CVD mortality and morbidity was still associated with reduced risks for arsenic. Arsenic methylation profiles appeared to become more efficient among subjects after cessation of long-term exposure to high levels of arsenic. Besides, this study also illustrated significant gene-gene interaction and gene-environment on early effect markers for CVD. These results may have implications for arsenic mediation strategies in areas currently exposed to potentially harmful levels of arsenic in drinking water. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T06:55:36Z (GMT). No. of bitstreams: 1 ntu-100-D94842003-1.pdf: 2208277 bytes, checksum: bc2f0972944b126d5ac9344b14f7a4a0 (MD5) Previous issue date: 2011 | en |
dc.description.tableofcontents | 誌 謝 1
中文摘要 2 Abstract 3 Chapter 1: Introduction 10 1.1 Global endemic of chronic arsenic poisoning 10 1.2 Nature history of cardiovascular disease (CVD) 11 1.3 Arsenic-related CVD 11 1.4 Genetic factors associated with arsenic metabolism and CVD 12 1.4.1 Arsenic metabolism genes 12 1.4.2 Atherosclerosis- and CVD-related genes 13 1.4.3 Other genes may linked to arsenic-related CVD 13 1.5 Arsenic-related early effect biomarkers for CVD 14 1.6 Specific aims and hypotheses 16 Chapter 2: Materials and Methods 18 2.1 Study area and population 18 2.2 Measurement of arsenic exposure 18 2.3 Questionnaire interview 19 2.4 Biochemical measurements 19 2.5 Genotyping 20 2.6 Physical examination 21 2.7 Ascertainment of cause of death 21 2.8 Statistical analysis 22 Chapter 3: Synergistic effect of polymorphisms of Paraoxonase gene cluster and arsenic exposure on electrocardiogram abnormality 23 3.1 Summary 23 3.2 Introduction 24 3.3 Methods 26 3.3.1 Study area and population 26 3.3.2 Data collection 26 3.3.3 Physiological Evaluation 27 3.3.4 SNP selection and genotyping 27 3.3.5 Statistical analysis 28 3.4 Results 28 3.4.1 Univariate SNPs association analysis 29 3.4.2 Haplotype analysis and association with ECG abnormality 29 3.4.3 Synergistic association of PON haplotype and arsenic on ECG abnormality 30 3.5 Discussion 30 Chapter 4: Arsenic-related lactate dehydrogenase (LDH) elevation and cardiovascular mortality in arsenic-endemic and non-endemic areas of southwestern Taiwan 42 4.1 Summary 42 4.2 Introduction 43 4.3 Methods 45 4.3.1 Study area and population 45 4.3.2 Data collection 46 4.3.3 Biochemical measurements and urinary arsenic species 46 4.3.4 SNP selection and genotyping 47 4.3.5 Ascertainment of causes of death 47 4.3.6 Statistical analysis 48 4.4 Results 49 4.4.1 Univariate association of abnormal LDH elevation 49 4.4.2 Multiple association of abnormal LDH elevation 50 4.4.3 Association between abnormal LDH elevation and mortality 51 4.5 Discussion 51 Chapter 5: Arsenic metabolism, lactate dehydrogenase and electrocardiogram abnormality among residents in arseniasis-endemic and non-endemic areas of southwestern Taiwan 63 5.1 Summary 63 5.2 Introduction 64 5.3 Methods 65 5.3.1 Study area and population 66 5.3.2 Data collection 66 5.3.3 Biochemical measurements and urinary arsenic species 67 5.3.4 Assessment of ECG abnormality 68 5.3.5 Statistical analysis 68 5.4 Results 69 5.5 Discussion 70 Chapter 6: Conclusion and future prospects 79 References 83 | |
dc.language.iso | en | |
dc.title | 台灣西南沿海高砷暴露地區與非暴露地區之心電圖異常與心血管疾病死亡率:基因與環境交互作用之研究 | zh_TW |
dc.title | Electrocardiogram (ECG) abnormality and cardiovascular mortality among residents in arseniasis-endemic and non-endemic areas of southwestern Taiwan: A study of gene-gene and gene-environment interactions | en |
dc.type | Thesis | |
dc.date.schoolyear | 99-1 | |
dc.description.degree | 博士 | |
dc.contributor.coadvisor | 陳建仁(Chien-Jen Chen),王淑麗(Shu-Li Wang) | |
dc.contributor.oralexamcommittee | 李文宗(Wen-Chung Lee),蕭朱杏(Chuhsing Kate Hsiao),邱弘毅(Hung-Yi Chiou) | |
dc.subject.keyword | 砷暴露,缺血性心臟病,心電圖,乳酸去氫酶,巴拉松酶,三價砷甲基化酶,榖胱苷,肽,硫轉移酶, | zh_TW |
dc.subject.keyword | Arsenic exposure,Ischemic heart disease,Electrocardiogram,Lactate dehydrogenase,Paraoxonase,Arsenic methyltransferase,Glutathione S-transferases omega, | en |
dc.relation.page | 94 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2011-02-09 | |
dc.contributor.author-college | 公共衛生學院 | zh_TW |
dc.contributor.author-dept | 流行病學與預防醫學研究所 | zh_TW |
顯示於系所單位: | 流行病學與預防醫學研究所 |
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ntu-100-1.pdf 目前未授權公開取用 | 2.16 MB | Adobe PDF |
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