THE GENETICS OF ALCOHOLISM: IS THERE AN INHERITED SUSCEPTIBILITY TO ALCOHOL-RELATED PROBLEMS?
THE GENETICS OF ALCOHOLISM: IS THERE AN INHERITED SUSCEPTIBILITY TO ALCOHOL-RELATED PROBLEMS?
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酗酒的遗传学：是否存在与酒精相关的问题的遗传易感性？
DOI：
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发表时间：
1983
期刊：
影响因子：
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通讯作者：
Roger Williams
中科院分区：
文献类型：
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作者：
J. Saunders;Roger Williams
酒精中毒和酒精相关疾病有明显的家族倾向。多年来，关于这是否代表遗传特征的传播或家庭环境对饮酒行为的影响，一直存在相当大的争论。对收养儿童和单卵双胞胎与双卵双胞胎的研究表明，遗传对饮酒习惯以及（至少在男性中）与酗酒相关的心理社会问题的发生有适度但明确的影响。有两种类型的酗酒的证据，一种是高度遗传的，另一种是遗传程度较低，需要环境压力才能表现出来。虽然酒精的代谢和它的许多生理作用部分是由遗传决定的，但这种遗传影响的表达机制尚不清楚。没有生物学标志物与酒精中毒倾向有令人信服的联系，但在50%的东方人群中出现的醛脱氢酶同工酶的缺乏与酒精潮红反应有关，这可能对酒精消费有不良影响。这也许可以解释为什么东方国家酗酒问题发生率低。
长期以来，遗传因素一直被认为是慢性酒精消耗的身体后遗症（如肝硬化和心肌病）易感性变化的原因。妇女在饮酒时间较短和每日饮酒量低于男子后，会出现许多酒精中毒并发症，特别是肝病，这部分与身体大小和组成以及激素状态的差异有关。几种组织相容性（HLA）抗原与肝硬化的易感性有关。大多数人的相关性相对较弱，但HLA-B8和DR 3与肝硬化的加速发展有关，可能是通过刺激对酒精损伤的肝细胞的细胞毒性免疫反应。对于哪些遗传因素可能导致其他酒精相关疾病，我们知之甚少。
进一步研究遗传因素影响酒精中毒发展及其并发症易感性的机制可能有助于确定干扰这些过程的药物。对于高度遗传性酒精中毒患者的家庭成员，完全戒酒可能是明智的。在更多地了解个人饮酒的安全限度之前，应该建议每个人保持低于80克酒精/天（男性）或40克/天（女性）。
Alcoholism and alcohol-related disorders have a pronounced familial tendency. There has been considerable debate over many years as to whether this represents transmission of genetic traits or the influence of family environment on drinking behaviour. Studies of adopted children and of monozygotic compared with dizygotic twins show a modest but definite genetic influence on drinking habits and, at least in men, on the occurrence of psychosocial problems related to alcohol abuse. There is evidence for two types of alcoholism, one that is highly heritable and another that shows a lesser degree of inheritance and requires environmental stressors for it to be manifest. The mechanisms by which such genetic influences are expressed are unknown although the metabolism of alcohol and many of its physiological effects are partly genetically determined. No biological markers have been associated convincingly with a predisposition to alcoholism but absence of an isoenzyme of aldehyde dehydrogenase, which occurs in 50% of Oriental populations, has been related to the alcohol-flush reaction which may have an aversive effect on alcohol consumption. This may explain the low incidence of alcohol problems in Oriental countries.
Genetic factors have long been thought to be responsible for the variation in susceptibility to the physical sequelae of chronic alcohol consumption such as cirrhosis and cardiomyopathy. Women develop many complications of alcoholism, especially liver disease, after a shorter period of drinking and at a lower daily alcohol intake than men, and this is partly related to differencesin body size and composition and in hormonal status. Several hiitocompatibility (HLA) antigens have been linked to susceptibility to cirrhosis. The association for most is relatively weak but HLA-B8 and DR3 are associated with accelerated development of cirrhosis, possibly by stimulating cytotoxic immune reactions to alcohol-damaged liver cells. Little is known about what genetic factors might predispose to other alcohol-related diseases.
Further work into the mechanisms by which genetic factors influence the development of alcoholism and susceptibility to its complications may help identify agents that interfere with these processes. Total abstinence from alcohol may be advisable for family members of subjects with the highly heritable form of alcoholism. Until more is known about individual safe limits for drinking everyone should be advised to keep below 80g alcohol/day (for men) or 40g/day (for women).