AGT基因、職業噪音暴露及其交互作用與高血壓之相關研究

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题名:	AGT基因、職業噪音暴露及其交互作用與高血壓之相關研究 Angiotension Gene,Occupational Noise Exposure and their Interaction in the Development of Hypertension.
作者:	鄭伉吟;Kang-Yin Chang
贡献者:	公共衛生學院職業安全衛生學系碩士班
关键词:	高血壓;噪音;單一核苷酸變異;交互作用;hypertension;noise;AGT M235T;interaction
日期:	2010
上传时间:	2010-09-29 12:04:30 (UTC+8)
摘要:	高血壓是一種病因複雜的疾病，它可能是由遺傳和環境相互影響而造成的。許多研究發現，位於Angiotensinogen(AGT)基因中有單一核苷酸多型性的變異(Single Nucleotide Polymorphism；SNP)，此SNP與高血壓有關。許多研究認為噪音與高血壓的發生有關，目前台灣雖有少數研究團隊在探討AGT基因的多型性(polymorphism)或是噪音對心血管疾病的影響，但基因與噪音共同暴露對罹患高血壓是否有關還未有學者進行研究。本研究目的如下:(1)以航太工業勞工為基礎進行世代研究(cohort study)，以了解勞工長期暴露於不同噪音之工作環境與罹患高血壓是否有關。(2)進一步分析AGT M235T基因多型性的變異是否與罹患高血壓有關。(3)最後探討長期暴露於不同噪音之工作環境與AGT M235T基因多型性對罹患高血壓是否有交互作用。本研究為動態性世代研究(Dynamic cohort study)，勞工自進入該公司起即成為本世代研究之研究對象，離職、退休或死亡則自研究中刪除。首先經勞工同意後發放生活習慣問卷及蒐集周邊靜脈血液進行DNA萃取，並實地測量該公司各作業廠所噪音值，扣除無基因型及無工作環境噪音值後將912人納入本研究，研究對象平均追蹤時間長達12年。本研究將利用分析出之基因型(MM、MT、TT)與噪音值(高噪音暴露：>80 dBA、中噪音暴露：80-65 dBA、低噪音暴露：64-50 dBA、參考族群：49-40 dBA)以卡方儉定、普瓦松回歸分析等統計方法進行統計分析，以了解長期噪音暴露與AGT M235T基因多型性與罹患高血壓是否有關。研究期間共有238位研究對象罹患高血壓(發生率為26.1%)。在基本資料方面，年齡較大、有飲酒習慣和鹽份攝取量較高、三酸甘油脂過高、高密度脂蛋白過低以及男性與罹患高血壓有顯著相關(p-value < 0.05)。以攜帶MM基因型者為參考族群，使用普瓦松(Poisson regression)回歸分析調整干擾因子後發現，攜帶TT基因型之勞工與罹患高血壓有顯著相關，其相對危險性為1.77 ??95% C.I: 1.24-2.51?矷A攜帶MT基因型者與參考族群相比，罹患高血壓的風險則無則差別，為1.10 ??95% 0.71-1.72?矷C以暴露時間3-15年進行噪音暴露程度與高血壓相關性分析，調整干擾因子後發現中噪音暴露、高噪音暴露與罹患高血壓皆有顯著相關，其相對危險性分別為2.32 ??95% C.I: 1.38-3.90?秅?2.53 ??95% C.I: 1.14-5.65?矷A若暴露時間大於15年之勞工無論暴露於何種作業環境噪音值與罹患高血壓則無顯著相關性存在。將MM與TM基因型及高噪音與中噪音合併後，以攜帶MM或TM基因型且暴露小於50 dB之勞工當作參考族群，調整後發現攜帶MM或TM基因型且暴露噪音大於65 dB者與罹患高血壓有顯著相關，相對危險性為3.04 ??95% C.I: 1.45-6.42?矷A攜帶TT基因型且暴露小於50 dB者與罹患高血壓則無相關性存在，相對危險性為1.56 ??95% C.I: 0.86-2.83?矷A攜帶TT基因型且暴露噪音大於65 dB者與罹患高血壓有顯著相關，相對危險性為3.73 ??95% C.I: 1.84-7.56?矷C以相加模式分析噪音與基因間交互作用關係，發現攜帶TT且暴露於高噪音下罹患高血壓之觀察可歸因危險性2.72大於期望可歸因危險性2.60，表兩者有正向之交互作用存在。本研究結果發現AGT M235T基因在此研究中是一個高血壓易感受基因，且3-15年之作業環境高噪音暴露(> 65 dB)也會顯著增患高血壓之風險，透過相加性交互作用也證明兩者間存在正向交互作用之關係。先前探討AGT M235T基因及高噪音暴露與高血壓相關性大部分是以橫斷研究或病例對照研究進行，研究結果可能會產生偏差，本研究以世代追蹤方式進行，因果關係較強，可避免研究結果產生誤差，且本研究結果針對攜帶AGT TT基因型與高噪音暴露對高血壓的影響也提供了更強而有力的證據。預防措施方面，相關單位應盡速透過教育、訓練計畫及工程控制降低噪音對高血壓的風險。 Hypertension is a complex multifactorial disease arrociated with genetic and environmental exposure. There are cumulative evidences that Angiotensinogen (AGT) gene single nucleotide polymorphisms (SNPs) were related to hypertension. In addition, chronic noise exposure may also associate with hypertension. The independent and joint effects of chronic noise exposure and angiotensinogen (AGT) gene on the development of hypertension have not been investigated. Previous studies of the effects of agiotension (AGT) and noise exposure on the risk of hypertension have mainly been cross-sectional or prevalent case-controls studies, where temporality constitutes problems. The study objectives are 1) to evaluate chronic noise exposure on the development of hypertension. 2) to determine whether or not the AGT M235T gene is associated with hypertension. 3) to evaluate the independent and joint effects of chronic noise exposure and angiotensinogen (AGT) gene on the development of hypertension. This study design was a dynamic cohort study conducted at a company in Taichang. At the cohort entry, we collected information on life habit and clinical check-up, and blood sample for determing DNA. The follow-up time was started from the dete of employment until the development of hypertension. We did not include the employee resigned, retired or died during the study period. The study population included 912 subjects without hypertension at baseline. The outcome of interest was development of hypertension during the study period. The average of follow-up time is 12 years. We constructed the chronic noise exposure based on the measurement of noise in working place and duration of exposure. The studied determinants were three AGT genotypes (TT, TM and MM) and four exposure categories based on the levels of noise representing high (>80 dBA), medium (80-65 dBA), low exposure (64-50 dBA), and the reference (49-40 dBA). We used Chi-square, ANOVA and Poisson regression to assess the relation between AGT M235T or choric noise exposure and the development of hypertension. A total of 238 (26.1%) subjects developed hypertension during the study period. The older age, alcohol consumption and higher daily salt intake, higher TG, lower HDL and female are more likely to develop hypertension. In Poisson regression adjusting for confounding, AGT TT genotype was significantly associated with the risk of hypertension with an adjusted incidence rate ratio of 1.77 (95% CI 1.24-2.51), but not for TM genotype (adjusted IRR 1.10 95% CI 0.71-1.72) as compared with MM genotype. The incidence of hypertension was related to the medium (adjusted incidence rate ratio: IRR 2.32 and 95% CI 1.38-3.90) and high exposure (IRR 2.53 95% CI 1.14-5.65) categories during 3-15 years exposure. The risk of developing hypertension exposure to noise after 15 years was not related to the three exposure indicators. Subjects with AGT (MM and TM combined) and exposure to noise above 65 dBA significantly increased the risk of hypertension with an adjusted incidence rate ratio of 3.04 (95% CI 1.45- 6.42), the effect of noise exposure below 50 dBA with TT genotype also increased with an IRR of 1.56 (95% CI 0.86-2.83), subjects with both TT genotype and exposure to noise above 65 dBA, the adjusted IRR of hypertension was 3.73 (95%CI 1.84-7.56), compared with the reference category. The expected attributable risk was 2.60, thus the observed attributable risk of TT genotype and High or medium exposure to noise was 2.72 more than expected on the basis of their additive independent effects. The results strengthen the evidence on the independent effects of AGT and noise exposure during 3-15 years of follow-up. Previous knowledge of the relation between AGT and noise and the risk of hypertension comes mainly from cross-sectional studies with establishment casual relationship is the most important threat of validity. In the present cohort study, we were able to avoid the threat to validity. The results also provide further evidence that subjects with both AGT TT genotype and high noise exposure which make them more susceptible to develop hypertension. Preventive intervention, such as education and training programs, engineering control to reduce noise levels against hypertension should be acted without any delay.
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