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  • 學位論文

台灣烏腳病盛行地區高血壓盛行率與一氧化氮合成酵素基因多型性之關係

The Relationship between Nitric Oxide Synthase Gene Polymorphism and Hypertension in Blackfoot Disease Hyperendemic Area in Taiwan

指導教授 : 薛玉梅
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摘要


本研究為探討烏腳病盛行地區居民高血壓盛行率與內皮的一氧化氮合成酵素基因多型性的關係。係以烏腳病高盛行地區的嘉義縣布袋鎮好美、復興與新民三里為研究地區。民國77至78年間所有年滿30歲且每週至少居住當地五天的現住居民為研究對象,經由受過標準化訪視訓練的訪視員利用結構式問卷進行家庭訪視。問卷內容包括人口學資料、居住史、飲水史與生活習慣等變項。此外,在民國80,82與86年各進行一次健康檢查篩檢高血壓與糖尿病患者,並以真空採血器採取受檢者血液樣本。血清與白血球分離後予以-70℃冷凍貯存,以備血清中臨床生化檢查和萃取白血球的DNA,進行內皮的一氧化氮合成酵素基因多型性分析。本研究利用82年所收集研究對象的生物檢體,隨機選取有尿液砷物種資料共327人之血液樣本進行內皮的一氧化氮合成酵素基因多型性之分析。白血球萃取的DNA,利用聚合酵素連鎖反應(PCR),再使用BanⅡ酵素做限制片段長度多型性(RFLP),分析內皮的一氧化氮合成酵素基因多型性。研究結果發現,居住在烏腳病盛行地區的居民,血壓正常者與高血壓者之基因座分布並無顯著差異。在調整內皮的一氧化氮合成酵素基因型態及砷代謝能力後,年齡、性別、身體質量指數、累積砷暴露、三酸甘油脂或低密度脂蛋白膽固醇與高血壓危險對比值呈顯著正相關。在調整年齡、性別、身體質量指數與內皮的一氧化氮合成酵素基因多型性後,累積砷暴露越高且無機砷代謝百分比越高者,高血壓危險對比值顯著增加。內皮的一氧化氮合成酵素基因座為野生型者(eNOS codon 298 (wt/wt)),高血壓危險對比值與慢性砷暴露及其他傳統危險因子有顯著相關。內皮的一氧化氮合成酵素基因座為變異型異質結合子(eNOS codon 298 (wt/vt))與變異型同質結合子(eNOS codon 298 (vt/vt))者,慢性砷暴露增加與砷代謝二級指標越差者,高血壓危險對比值也增加,雖未達統計上顯著性,但可發現內皮的一氧化氮合成酵素基因多型性有變異者高血壓的危險對比值比野生型者偏高。

並列摘要


This study was conducted to explore the relationship among nitric oxide synthase gene polymorphism, arsenic methylation capability, and the prevalence of hypertension in blackfoot disease hyperendemic area in Taiwan. Three villages, Homei, Fuhsin and Hsinming of Putai Township on the southwestern coast of Taiwan Island were selected as the study area. The residents aged 30 or more years old, who lived at least 5 days a week in the villages were recruited into this study from January to February 1989. Each study subject was personally interviewed by well-trained interviewers with standardized interview techniques and with a structured questionnaire. The history of living in the arseniasis endemic area and duration of drinking artesian well water, together with life style variables including alcohol drinking, cigarette smoking and dietary habit, as well as personal and family history of disease were obtained in the interview. In addition, the study subjects received physical examination and the fasting bloods were collected. Serum and buffy coat were separated and stored in -70℃ for the analysis of clinical biochemistry indies and nitric oxide synthase gene polymorphism. The serum samples of 327 study subjects were collected from 1993 who had urinary arsenic species data were randomly recruited as study subjects in this study. DNA was extracted from buffy coat to analyze nitric oxide synthase(eNOS) gene polymorphism utilizing polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) We found no difference in the eNOS gene polymorphism between hypertension patients and normal tension controls. On the other hand, we found that age, sex, body mass index (BMI), cumulative arsenic exposure were significantly positively related with the risk of hypertension after adjustment with eNOS gene polymorphism and arsenic metabolism capability. The higher the cumulative arsenic exposure and the lower arsenic metabolism capability increase the risk of hypertension after adjustment with age, sex, BMI, eNOS gene polymorphism. In the eNOS codon 298 (wt/wt), the odds ratio of hypertension was related with age, sex, BMI, and arsenic metabolism capability. But, the eNOS codon 298 (wt/vt) and eNOS codon 298 (vt/vt) did not related. On the other hand, in the eNOS codon 298 (wt/wt), the higher the cumulative arsenic exposure and the lower arsenic metabolism capability increase the risk of hypertension after age, sex, BMI, eNOS gene polymorphism adjustment. The same result was shown in the eNOS codon 298 (wt/vt) and eNOS codon 298 (vt/vt).

參考文獻


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被引用紀錄


陳惠雯(2002)。台灣烏腳病盛行地區高血壓與含錳超氧歧化酵素基因多形性之相關性研究〔碩士論文,臺北醫學大學〕。華藝線上圖書館。https://www.airitilibrary.com/Article/Detail?DocID=U0007-1704200714494824

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