[ 摘要 ]

酒癮包括酒精濫用及酒精依賴，不但會引起種種生理上的合併症以至於死亡，甚至引起嚴重的社會問題，其成癮機制涵蓋環境、心理、生物體質及神經生理等多層面的因素。有關酒癮的研究早在1980年代學者們利用家族研究、領養研究、雙胞胎研究，發現遺傳因素在酒癮致病因上有重要的角色。在諸多遺傳誘發因素中，酒精代謝是重要的生物決定因子，直接或間接影響酒癮的形成。

ADH、ALDH基因多型性所製造的，分別為乙醇及乙醛之主要代謝之一。十年來Thomasson HR.等人認為ADH2*2及ALDH2*2基因，於亞洲人種皆具有防止酒癮形成的保護作用。為研究於台灣這兩個保護基因與酒癮之關係，我們依台灣漢民族、泰雅、阿美3大族群以91位酒癮依賴患者及91位非酒癮對照組作基因型之鑑定。

我們發現台灣漢民族與泰雅、阿美族群在這兩個基因呈現不同的分佈。ADH2*2及ALDH2*2於酒癮患者和對照組之間只有台灣漢民族存顯著的差異(p=0.001,p=0.002)，而泰雅、阿美沒有存在有意義的不同(p=0.2~0.7)。ADH2*2及ALDH2*2於台灣漢民族的確皆具有保護作用，且同時擁有ADH2*2和ALDH2*2保護基因時台灣漢民族也的確可以避免或減少酒癮之發生 (p=0.001)。於本研究ALDH2*2仍然扮演著酒癮形成的保護角色；但我們發現在高酒癮盛行率且高ADH2*2的泰雅、阿美族群中，ADH2*2卻無任何保護作用，驗證了ADH2*2基因並不是酒癮保護基因。

[ 英文摘要 ]

Alcohol use disorder includes alcohol abuse and alcohol dependence. It may give rise to death and critical social problem. Alcoholism is believed to be a multifactorial, polygenic disorder involving complex gene-with-gene and gene-with-environment interactions. Family, adoption, and twin studies suggest the involvement of hereditary component in alcoholism. The genes that encode the alcohol metabolism are important biological determinants that can significantly influence drinking behavior and the development of alcoholism.

Molecular genetic research into the alcoholism has drawn attention to the important role of alcohol- and acetaldehyde-metabolizing enzymes. The alcohol dehydrogenase(ADH) and aldehyde dehydrogenase(ALDH) that metabolize ethanol exhibit functional polymorphism. For the last several decades, Thomasson et al. suggested that the ADH2*2 and ALDH2*2 variant reduces the risk of alcohol dependence among Asian populations. To investigate the possible interactions among these protective genes in Taiwan, we determined the genotypes of the ADH2 and ALDH2 loci of the ethnically matched alcoholic (n=91) and normal controls (n=91) for the three largest ethnic groups (Han, Atayal, Ami) living in Taiwan.

There are differences in the distribution of ADH2*2 and ALDH2*2 among Han, Atayal and Ami ethnic groups. For ADH2*2 and ALDH 2*2 in alcoholics and control group, only Han ethnic group showed significant difference (p=0.001,p=0.002), whereas Atayal and Ami showed no significant difference (p=0.2~0.7). In Han ethnic group, ADH2*2 and ALDH2*2 displayed protective effect. Thus, the coexistence of ADH2*2 and ALDH2*2 protective genes in Han ethnic group correlated with the low possibility of alcohol dependence (p=0.001). In conclusion, we show that ALDH2*2 also plays a protective role in alcoholism. Furthermore, ADH2*2 can’t have any protective effect to the high alcohol prevalence of Atayal and Ami ethnic groups. The results suggest that ADH2*2 genotype is not a protective factor in alcoholism as previously suggested.