台灣鄉村居民砷及鉛暴露與血壓之相關：含錳超氧歧化酶MnSOD及核酸糖解酶OGG1基因的可能效應

Association of Arsenic and Lead Exposure and Blood Pressure in Taiwanese Rural Residents: Possible Effects of Manganese Superoxide Dismutase MnSOD and 8-Oxoguanine-DNA Glycosylase OGG1 Genes

林錦秀(Chin-Hsiu Lin)

指導教授 ： 翁瑞宏

中山醫學大學/健康管理學院/公共衛生學系碩士班/碩士(2009年)

https://doi.org/10.6834/CSMU.2009.00086

摘要

高血壓 (hypertension) 是心血管疾病的重要決定因子，並且環境與基因的交互作用可能貢獻於高血壓的產生。來自環境的重金屬 (heavy metal) 暴露已經被報告可導致細胞的氧化傷害，並且氧化壓力可能與高血壓的發展具有相關；重要的是，砷 (arsenic) 與鉛 (lead) 暴露已經被建議可導致高血壓。然而，當砷與鉛金屬同時存在下之心血管疾病的確實機制則較不清楚。此外，含錳超氧化物歧解酶 (manganese superoxide dismutase [MnSOD]) 是對抗超氧化自由基 (superoxide radicals) 的第一道防線，而8-oxoguanine-DNA glycosylase (OGG1) 也是修補氧化性DNA傷害的主要DNA糖解酶；但是對於承受砷及鉛暴露的個體，其MnSOD與OGG1基因於高血壓上的效應並未被探討。因此，我們執行一個斷代研究 (cross-sectional study) 來探討是否個體之尿中砷與鉛濃度相關於高血壓發生危險；並且是否在砷或鉛暴露的個體中，MnSOD與OGG1基因型是較易感受性於高血壓的發展。我們使用原子吸收光譜儀分析 (atomic absorption spectrometry) 測量240名台灣鄉村居民的尿中砷與鉛濃度，每名對象也被評估其血壓、身高、體重、身體質量指數 (body mass index)、膽固醇 (cholesterol)、三酸甘油酯 (triglyceride)、與尿酸 (uric acid)。問卷被執行以獲得人口學資料、生活型態、醫療與職業史；MnSOD與OGG1基因型則是以聚合酶鏈鎖反應為基礎的限制酵素片段長度多形性 (polymerase chain reaction based restriction fragment length polymorphism) 來判定。結果顯示一個顯著的劑量效應關係 (dose-response relationship) 本研究對象之尿液砷濃度與高血壓危險之間 (P = 0.034，test for trend)。然而在研究對象中，尿液鉛濃度與高血壓危險之間沒有呈現顯著相關。此外，擁有高尿中砷與MnSOD Ala-Ala/Val-Ala基因型者具有明顯的高血壓之較高危險，相較於擁有低尿中砷與MnSOD Val-Val基因型者 (危險對比值，odds ratio [OR] = 3.2, 95%信賴區間，95% confidence interval [C. I.] = 1.4-7.5)；相同的，擁有高尿中砷與OGG1 Cys-Cys基因型者具有高血壓之較高危險，相較於擁有低尿中砷與OGG1 Ser-Ser/Ser-Cys基因型者 (OR = 2.8, 95% C. I. = 1.0-7.4)。這些結果建議著，砷暴露可能貢獻於台灣鄉村居民的高血壓發展；並且個體攜帶易感受性之MnSOD與OGG1基因型可能容易傾向於因砷暴露而導致的高血壓之增加危險。

關鍵字

高血壓 ； 砷 ； 鉛 ； MnSOD基因 ； OGG1基因

並列摘要

Hypertension is an important determinant of cardiovascular diseases. Genetic and environmental interaction may attribute to the formation of hypertension. Heavy metal exposure from environment has been reported to result in cellular oxidative damage, and oxidative stress might be related to the development of hypertension. Importantly, arsenic and lead exposure has been suggested to cause hypertension. However, little is known about the exact mechanism under cardiovascular disease of arsenic and lead metals when they are present together. In addition, the manganese superoxide dismutase (MnSOD) is the first line of defense against superoxide radicals. The 8-oxoguanine DNA glycosylase (OGG1) is also the major DNA glycosylase for the repair of oxidative DNA lesions. The effect of MnSOD and OGG1 genes on hypertension in people with arsenic and lead exposure has not been investigated. Therefore, we performed a cross-sectional study to investigate whether urinary concentrations of arsenic and lead in people were associated with hypertension risk, and whether MnSOD and OGG1 genotypes were more susceptible to hypertension development in arsenic or lead-exposed individuals. We measured urinary levels of arsenic and lead for 240 Taiwanese rural residents using atomic absorption spectrometry. Blood pressure, body height, body weight, body mass index, cholesterol, triglyceride, and uric acid were also assessed for each subject. Questionnaires were administered to obtain demographic data, lifestyles, and histories of medical, and occupation. The genotypes of MnSOD and OGG1 were identified by the polymerase chain reaction based restriction fragment length polymorphism. Results showed a significant dose-response relationship between urinary arsenic level and hypertension risk in our subjects (P = 0.034, test for trend). However, no significant association between urinary lead level and hypertension risk in our subjects was revealed. In addition, subjects experienced high urinary arsenic and MnSOD Ala-Ala/Val-Ala genotypes had an obviously higher risk of hypertension compared to those experienced low urinary arsenic and MnSOD Val-Val genotype (odds ratio [OR] = 3.2, 95% confidence interval [C. I.] = 1.4-7.5). Similarly, subjects experienced high urinary arsenic and OGG1 Cys-Cys genotype had a higher risk of hypertension compared to those experienced low urinary arsenic and OGG1 Ser-Ser/Ser-Cys genotypes (OR = 2.8, 95% C. I. = 1.0-7.4). These results suggest that arsenic exposure may attribute to the hypertension development in Taiwanese rural resident; and individuals with susceptible MnSOD and OGG1 genotypes may prone an increased risk of hypertension elicited by arsenic exposure.

並列關鍵字

Hypertension ； Arsenic ； Lead ； MnSOD gene ； OGG1 gene

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