Matsushita Sachio, Higuchi Susumu
National Hospital Organization, Kurihama Medical and Addiction Center, Yokosuka, Kanagawa, Japan.
Am J Addict. 2017 Aug;26(5):469-476. doi: 10.1111/ajad.12477. Epub 2017 Jan 18.
Epidemiological studies consistently find that Asian populations report lower rates of alcohol use disorders (AUD) compared with other racial groups. These differences result from a variety of biological, genetic, and environmental influences, some of which are related to the metabolism of alcohol. We will review several studies of these metabolic factors, including several alcohol clamping studies conducted in our laboratory, that provide further insight into the role of the alcohol metabolizing genes and drinking behavior among Japanese drinkers.
This manuscript reviewed studies investigating genetic variations of alcohol metabolizing enzymes among Asians and several mechanisms by which these genes are thought to give rise to differences in rates of alcohol dependence.
The inactive aldehyde dehydrogenase 2 (ALDH2) and highly active alcohol dehydrogenase-1B (ADH1B) genes are protective factors for the development of AUD. The inactive ALDH2 provides its protective effect through the accumulation of acetaldehyde after consuming alcohol, resulting in unpleasant effects, and heightened sensitivity to alcohol. However, the suppressive effects of inactive ALDH2 and highly active ADH1B for AUDs are only partial and interact with other factors, such as personality traits, psychiatric comorbidities, and environmental factors.
While Asians are excellent models for the study of certain genetic effects on the development and consequences of AUD, few clinical studies of this population have been conducted. Further exploration of the interactions between various genetic, individual, and environmental factors influencing drinking behavior and, thus affecting the risk of AUD, would enhance our understanding of how alcohol-related problems develop.
The heterozygous ALDH2*1/*2 genotype has only partial effects on limiting drinking behavior, suggesting the potential interaction with other factors. Therefore AUD patients with inactive ALDH2 may be a useful model to identify and to test a variety of other risk factors of AUD. (Am J Addict 2017;26:469-476).
流行病学研究一致发现，与其他种族群体相比，亚洲人群报告的酒精使用障碍（AUD）发生率较低。这些差异源于多种生物、遗传和环境影响，其中一些与酒精代谢有关。我们将回顾几项关于这些代谢因素的研究，包括在我们实验室进行的几项酒精钳夹研究，这些研究进一步深入了解了酒精代谢基因在日本饮酒者饮酒行为中的作用。
本手稿回顾了调查亚洲人酒精代谢酶基因变异的研究，以及这些基因被认为导致酒精依赖率差异的几种机制。
无活性的乙醛脱氢酶2（ALDH2）和高活性的乙醇脱氢酶-1B（ADH1B）基因是AUD发生的保护因素。无活性的ALDH2通过饮酒后乙醛的积累发挥其保护作用，导致不适反应，并增强对酒精的敏感性。然而，无活性的ALDH2和高活性的ADH1B对AUD的抑制作用只是部分的，并且与其他因素相互作用，如人格特质、精神共病和环境因素。
虽然亚洲人是研究某些基因对AUD发生和后果影响的优秀模型，但针对该人群的临床研究很少。进一步探索影响饮酒行为从而影响AUD风险的各种遗传、个体和环境因素之间的相互作用，将增进我们对酒精相关问题如何发生的理解。
杂合子ALDH2*1/*2基因型对限制饮酒行为只有部分作用，表明其与其他因素可能存在相互作用。因此，携带无活性ALDH2的AUD患者可能是识别和测试AUD各种其他风险因素的有用模型。（《美国成瘾杂志》2017年；26:469 - 476）
