砷暴露地區居民發炎因子基因多形性與頸動脈粥狀硬化之相關性研
究
A study on association between carotid atherosclerosis and inflammatory gene polymorphisms among residents in arsenic-endemic area
中文摘要
動脈粥狀硬化已知為一發炎性的疾病，且是導致腦血管疾病、心血管疾病及週邊 血管疾病的主要次臨床症狀，而砷與前述這些疾病的相關性已經證實。本研究為 探討砷暴露與發炎因子基因多形性對於頸動脈粥狀硬化的獨立及交互作用之關
係。由民國86 年於蘭陽盆地礁溪、壯圍、冬山及五結四鄉中的十八個村所進行
之四十歲以上居民健康檢查且接受過杜卜勒超音波（Duplex ultrasonography）頸 動脈超音波檢查的民眾作為研究母群。隨機選取以頸動脈內膜厚度（intima media thickness）大於 1.0 或斑塊指數大於 1 者共 332 人為病例組，對照組共 302 人，
進行發炎因子包括細胞激素【白血球介素-1 接受體拮抗者（IL-1RN）、腫瘤壞死 因子（TNF-α）】、化學激素【單核球化學趨附蛋白-1（MCP-1）】及黏附因子【E- 選擇性蛋白（E-selectin）、細胞內黏附分子-1（ICAM-1）】等基因多形性的分析。
利用標準化問卷收集研究對象之基本人口學資料並測量其生化值。將萃取出的 DNA 利用聚合酵素連鎖反應（Polymerase chain reaction, PCR）及限制酵素作限 制片段長度多形性（Restriction fragment polymorphism, RFLP）來進行各種發炎 因子相關基因多形性分析。結果顯示在調整年齡、性別、抽菸、收縮壓以及總膽 固醇等傳統危險因子之後，各基因型變異者均會增加罹患動脈粥狀硬化的危險 性，但未達統計顯著水準。在與飲水砷濃度進行多變項分析後，則發現砷暴露與 各發炎因子基因多形性對於頸動脈粥狀硬化的影響可能是互相獨立的。進一步合 併飲水砷濃度小於等於50 μg/L 時，MCP-1 基因型為 G/G 者，其危險性是基因 型A/A 者的 3.9 倍，達統計顯著意義（p<0.01）。但是在飲水砷濃度大於50 μg/L 時，則危險性降低，顯示當環境暴露高於某一程度時，其對於疾病的影響大於基 因變異。
英文摘要
Carotid atherosclerosis is known as an inflammaroty disease and a subclinical syndrome of cerebrovascular, heart and peripheral vascular disease. The association between arsenic and these diseases has been proved through many epidemiological studies. The aim of the study is to investigate the association between carotid
atherosclerosis and genetic polymorphisms of inflammatory genes among residents in Lanyan Basin which was a newly confirmed arsenic-endemic area. Residents aged
≥40 years were recruited as study population. Each one was examined his/her carotid atherosclerosis by Duplex ultrasonography. A total of 332 subjects were randomly selected from study population as carotid atherosclerosis patients based on their helath examination reports with IMT ≥1.0 mm and plaque score ≥1. Controls were 302 subjects with IMT<1.0 mm and plaque score<1. Genetic polymorphisms of IL-1RN, TNF-α, MCP-1, E-selectin, and ICAM-1 were detected by PCR and RFLP. Logistic regression analysis was used to estimate multivariate-adjusted odds ratios and 95%
confidence intervals for various risk factors of carotid atherosclerosis.
The results showed that after adjustment for age, sex, tobacco smoking, systolic blood pressure and total cholesterol, the study subjects whose inflammatory gene with variant genetic type have non-significant increased risk for development of carotid atherosclerosis. Multivariate logistic regression analysis indicated that arsenic
exposure and genetic polymorphisms of inflammatory genes have independent effects on the risk of carotid atherosclerosis. For study subjects who drank well water with arsenic concentration lower than 50μg/L, those who with MCP-1 G/G genotype have four folds risk of carotid atherosclerosis than those who with A/A genotype after adjusting the carotid atherosclerosis related risk factors. However, the risk can not be found for study subjects who drank well water with arsenic concentration greater than 50μg/L. The study suggested that the arsenic exposure had more significant influence on carotid atherosclerosis than human susceptibility.
