飲酒習慣與酒精代謝基因對肝功能間之影響; Effect of Drinking Habits and CYP2E1 and ALDH2 Gene Polymorphisms on Hepatic Function

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Title:	飲酒習慣與酒精代謝基因對肝功能間之影響;Effect of Drinking Habits and CYP2E1 and ALDH2 Gene Polymorphisms on Hepatic Function
Authors:	王志偉;Zhi-Wei,Wang
Contributors:	中國醫藥學院環境醫學研究所
Keywords:	ALDH2;CYP2E1;飲酒習慣;肝功能;drinking habits;liver functions
Date:	1992
Issue Date:	2009-12-22 13:59:09 (UTC+8)
Abstract:	摘要根據研究顯示原住民飲酒盛行率較非原住民高，最近30年來更有上升10倍的趨勢，因為飲酒所造成的健康問題也一直困擾著原住民部落，一般認為飲酒習慣與遺傳有關。本研究是依據90年度和平鄉複合式篩檢所搜集的問卷調查資料與血液，探討飲酒習慣、個人基本特徵、疾病史與酒精代謝基因（ALDH2及CYP2E1）的關係，並進而探討飲酒習慣及酒精代謝基因的交互作用下，對肝功能的影響。研究對象為參與90年和平鄉複合式篩檢中，近半年具有飲酒習慣的鄉民共499人，依飲酒習慣分為三群，組一（Group I）為每周有1~2天飲酒，共289人，組二（Group II）為每周有3~4天飲酒，共110人及組三（Group III）為天天喝酒，共92人。做問卷調查與採血前，先徵求參與健檢者的同意與簽名，抽取的血液做為分析基因型用。而ALDH2及CYP2E1基因型測定是以聚合酶鏈鎖反應（PCR）增幅後，其各產物再分別使用限制酵素Mbo II及Pst I切割，經由電泳分離出各個不同的片段而得到該基因之基因型。結果顯示全體研究對象ALDH21/1基因型的頻率為83.2％、ALDH21/2型為16.2％、ALDH22/2型為0.6％；CYP2E1基因型c1/c1的頻率為70.6％、c1/c2型為24.2％、c2/c2型為5.2％。以族群做分層後，發現ALDH2在原住民與非原住民的分布上具有差異，非原住民帶有ALDH22對偶基因的比例較原住民高，但是原住民與非原住民在CYP2E1基因分布上則無明顯差異。以飲酒習慣而言，原住民有較高的飲酒比例（28.4％ vs. 22.1％），且女性原住民的飲酒比例為非原住民的2.3倍。在飲酒者中，若是帶有ALDH21對偶基因者，其肝功能異常的危險性是帶有ALDH22對偶基因的2.28倍。若是天天飲酒且帶有ALDH21者，其危險性更是每周喝1~2天且帶有ALDH22對偶基因的3.4倍。CYP2E1在飲酒習慣與對肝功能的影響上，則無明顯相關，皆未達到統計上的顯著差異。結論為飲酒習慣與ALDH22基因型有很強的相關性，且ALDH22對偶基因在和平鄉的飲酒者中為避免肝功能異常的可能保護因子，但是在CYP2E1基因則未發現與飲酒習慣和肝功能有相關; Abstract According to study results, drinking popularity of the aborigines was higher than non-aborigines. This tendency has been increased by 10 times for the past thirty years. As health problems resulted from wine drinking have always been a pain for aboriginal tribes, it is generally considered that such drinking habits are related to heredity. This research was based on the questionnaire surveys and blood samples collected from complex checkups conducted in He Ping Country in 2001 for an exploration of the relationships among drinking habits, basic characteristics of individuals, medical history and alcohol metabolism genes (ALDH2 and CYP2E1). In addition, the impact upon liver functions imposed by the correlation between drinking habits and alcohol metabolism genes was also discussed. Among the examinees who participated in complex checkups in He Ping Country in 2001, 499 people were drinking for the past half year. Three groups were divided according to drinking habits. There were 289 people in Group I who drank for 1 to 2 days per week. There were 110 people in Group II who drank for 3 to 4 days a week and Group III had 92 people who drank every day. The examinees were asked for their agreement and signature in advance for questionnaire surveys and blood drawing for genotype analysis. For ALDH2 and CYP2E1 genotype tests, individual product after increase of polymerase chain reaction (PCR) was cut by restriction enzymes Mbo II and Pst I and different fragments were separated via electrophoresis, which resulted in the genotype of the gene. The results showed that frequency of ALDH21/1 genotype was 83.2%, that of ALDH21/2 genotype was 16.2%, and that of ALDH22/2 genotype was 0.6%. For CYP2E1 genotype, frequency of c1/c1 type was 70.6%, that of c1/c2 type was 24.2% and that of c2/c2 type was 5.2%. After division of races, it was found that the distribution of ALDH2 was different between aborigines and non-aborigines. Non-aborigines with allele ALDH22 were more than aborigines; however there was no significant difference of CYP2E1 genetic distribution between aborigines and non-aborigines. For drinking habits, aborigines had a higher rate (28.4% vs. 22.1%) and female aborigine drinkers were 2.3 times more than female non-aborigines. If the drinkers had allele ALDH21, they took a higher risk of abnormal liver functions than the drinkers with allele ALDH22 by 2.28 times. Daily drinkers with ALDH21 took a even higher risk than the drinkers who drank for 1 to 2 days per week with allele ALDH22 by 3.4 times. There seemed no significant correlation between CYP2E1 and drinking habits or liver functions because no statistically significant difference was found. Conclusion: There is a tightly connected relationship between drinking habits and ALDH2*2 genotype, which becomes a potential protection factor for the drinkers in He Ping Country to prevent abnormal liver functions
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