不同飲水砷濃度居民脂蛋白元E、脂蛋白脂肪?之基因多形性、無機砷代謝能力與頸動脈粥狀硬化相關性研究

A stduy on the association between carotid atherosclerosis and genetic polymorphisms of apolipoprotein E and lipoprotein lipase, inorganic arsenic methylation capability among various arsenic exposure people.

周怡利(Yi-li Chou)

指導教授 ： 邱弘毅

臺北醫學大學/公共衛生暨營養學院/公共衛生學研究所/碩士(2000年)

摘要

近年來國人罹患血管相關疾病比率快速增加，導致血管病變的原因除了動脈粥狀硬化外，脂質代謝的異常也是的主要原因。過去的研究中，無機砷除了會引起癌症外，也會引起如糖尿病、高血壓、心血管與腦血管疾病。因此，本研究的目的是探討不同飲水砷濃度居民其無機砷代謝能力、脂蛋白元E及脂蛋白脂肪?基因多形性與頸動脈粥狀硬化的相關性。 本研究由宜蘭地區參與健檢的1692人中，依砷濃度分組隨機抽樣得304名個案，其中包括頸動脈粥狀硬化病人共157名，並利用年齡性別配對得健康對照共147人。個案的問卷內容有基本資料、飲水史、疾病史等；健康檢查的項目為身高、體重、血壓、視力、血液生化檢查及頸動脈超音波檢查等。研究中使用的暴露指標為外在暴露指標（飲水砷濃度）及內在暴露指標（尿液砷物種百分比）。藉由聚合?連鎖反應（PCR）技術放大脂蛋白元E、脂蛋白脂肪?的基因片段，再以限制片段長度多形性（RFLP）檢測各種基因的多形性。資料分析採用對數回歸計算各危險因子之危險對比值及95﹪信賴區間。 研究結果顯示，不論是低砷或高砷暴露組的病例及對照個案年齡分佈都在50-59.9歲。高血壓對罹患頸動脈粥狀硬化的危險性於低砷暴露時為11倍，而在高砷暴露則降為2倍，且都達到統計上顯著水準。在代謝能力指標中，當受高砷暴露時無機砷百分比對罹患頸動脈粥狀硬化有2倍危險性，並達統計水準。在低砷濃度組脂蛋白元E基因型為3/4、4/4，對於罹患頸動脈粥狀硬化有約8倍的危險性，也會有較高的總膽固醇及低密度脂蛋白膽固醇濃度，達統計上顯著水準；而此一基因型在高砷暴露組則為有前述之特性。另外脂蛋白脂肪?在低砷濃度組基因型為-/+，有較低的三酸甘油酯濃度，達統計上顯著水準；但在高砷暴露組則未見此一現象。總而言之，無機砷代謝能力不好，在高砷暴露族群與頸動脈粥狀硬化的危險性具正相關，但在低砷暴露族群不明顯。高砷暴露族群中與頸動脈粥狀硬化相關之危險因子如高血壓、脂蛋白元E及脂蛋白脂肪?的基因多形性所產生的危險效應會被高砷暴露加以修飾。

關鍵字

無機砷 ； 無機砷代謝能力 ； 頸動脈粥狀硬化 ； 脂蛋白元E ； 脂蛋白脂肪?

並列摘要

Recently, the prevalence rate of vascular diseases was increased fast. The major risk factors vascular diseases were atherosclerosis and abnormal lipid prolife in serum. In the previous studies, arsenic exposure would induce not only cancers but also vascular diseases including ischemic heart disease, cerebrovascular diseases, peripheral vascular diseases, diabetes mellitus, and hypertension. This study was carried out to evaluate the association between genetic polymorphisms of apolipoprotein E and lipoprotein lipase, inorganic arsenic methylation capability and carotid atherosclerosis among various arsenic exposure people. A total of 1692 residents of Lanyang Basin aged equal and greater then 40 years old were participated physical examination. Among them, a total of 304 study subjects including 157 atherosclerosis cases and 147 healthy control were recruited in this study. The structured questionnaire was used to collected sociodemographic factors, history of drinking water and family history of diseases. The items of physical examination included height, weight, blood pressure, blood biochemical examination and carotid atherosclerosis examined using Duppler ultrasonography. In this study, arsenic exposure indexes includes external（arsenic concentration in well water） and internal exposure（the percentage of unmethylated inorganic arsenic in urine）. Polymerase chain reaction（PCR）was used to amplify DNA to detect three apolipoprotein E（apoE） and two lipoprotein lipase（LPL） alleles. The amplified products were analyzed by HhaI and MnlI restriction fragment length polymorphism（RFLP）. Data analysis was performed with SAS software. Logistic regression model was used to obtain odds ratios（OR）of related risk factors and their 95% confidence intervals. Age of study subjects ranged from fifty to fifty-nine years old among case and control group. After adjustment for age and sex, an significant risk of carotid atherosclerosis was associated with hypertension for low-arsenic exposure group（OR=11）, and for high-arsenic exposure group （OR=2）. After adjustment for age and sex, an significant risk of carotid atherosclerosis was also associated with the high percentage of unmethylated inorganic arsenic in urine for high-arsenic exposure group（OR=2）. Stduy subjects with 3/4 and 4/4 variants of apoE had the highest concentration of total serum cholesterol and LDL cholesterol. In addition, an increased risk of carotid atherosclerosis was observed for those who with apoE variant types of 3/4 and 4/4 in the low-arsenic exposure group（OR=8）, but not in the high-arsenic exposure group. Study subjects with S447X variant of LPL had the lowest concentration of serum triglycerides in the low-arsenic group. In conclusion, high-arsenic exposure people who with low inorganic arsenic methylation capability would have increased risk of carotid atherosclerosis. The risk of carotid atherosclerosis risk of many factors including hypertension, genetic polymorphyisms of apoE and LPL and serum lipid profile might be modified by high-arsenic exposure.

並列關鍵字

inorganic arsenic ； inorganic arsenic methylation capability ； atherosclerosis ； apolipoprotein E ； lipoprotein lipase

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