GENETICS OF ALCOHOLISM IN AMERICAN INDIANS

美洲印第安人酗酒的遗传学

• 批准号: 2045529
• 负责人: RICHARD A DEITRICH
• 金额: $ 7.49万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-04-01 至 1994-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2045529
• 关键词: Asian Americans; Native Americans; alcohol dehydrogenase; alcoholic beverage consumption; alcoholism /alcohol abuse; aldehyde dehydrogenases; blood chemistry; blood pressure; body temperature; caucasian American; clearance rate; enzyme induction /repression; gene frequency; genetic disorder; heart rate; human population genetics; human subject; pathologic process; sign /symptom; vasodilation

There is increasing evidence that heredity plays a role in the development of alcoholism. The proposed research will examine some of the genetic antecedents of alcoholism in the American Indian population. While major research initiatives aimed at identifying the genes associated with alcoholism have begun in the Caucasian population, these studies largely exclude the Indian peoples. Among Orientals a single gene mutation has been identified which decreases alcohol intake. The mutation is a single base pair substitution that renders the enzyme aldehyde dehydrogenase (ALDH) inactive. Orientals with this gene develop a syndrome following alcohol ingestion with facial flushing, tachycardia and some nausea. While the mutation is common in Oriental populations (approx. 45%) it is seen in a very low proportion (approx. 4%) of Oriental alcoholics. Thus, it would appear that ALDH deficiency provides some immunity against the development of alcoholism. It is assumed that American Indians should show a similar frequency of this mutation, due to lineage to the Mongoloid race. The flushing reaction in Indians has long been assumed to occur. However, this has been documented in only a single report in 1972. While some researchers have found from 2-16% of various Indian tribes phenotypically deficient in ALDH, others have failed to find any American Indians with the ALDH deficiency. In pilot work we have identified some American Indians who self-report flushing reactions upon ingestion of ethanol. Thus, the nature of and the frequency of the flushing response in American Indians is not known. In addition, the relationship between ALDH activity and drinking levels has not been studied in American Indians. To investigate the possibility that American Indians have a genetic defect in the metabolism of alcohol we will: 1) Examine the qualitative and quantitative aspects of the flushing response to ingested alcohol by monitoring skin temperature, heart rate, blood pressure, blood acetaldehyde and alcohol levels in flushing and non-flushing American Indians as well as in Oriental and Caucasian control subjects. 2) Determine the phenotypic level of ALDH activity in flushing and non-flushing individuals from the three racial groups. 3) Determine whether or not American Indians have mutations in the genes which code for the alcohol metabolizing enzymes alcohol dehydrogenase (ADH) and ALDH. 4) Determine the interrelationships between the flushing response, ALDH activity, the rate of alcohol clearance, blood acetaldehyde levels, genotype of ADH and ALDH, the quantity/frequency of alcohol drinking behavior and family history of alcoholism through multivariate statistical techniques. 5) In the second year determine the population frequencies of the various ADH and ALDH geneotypes in several western Indian tribes (Blackfeet, Sioux, Navaho). The relationships between genotype, self-reported flushing, drinking practices and family history of alcoholism will be determined.

越来越多的证据表明遗传在发育中发挥着重要作用 酗酒。 拟议的研究将检查一些遗传因素 美洲印第安人酗酒的前因。 虽然主要 旨在识别相关基因的研究举措 酗酒已经开始在白种人中出现，这些研究主要 排除印度人民。 在东方人中，已发现一种单一基因突变，该突变会降低 酒精摄入量。 该突变是单碱基对替换， 使乙醛脱氢酶 (ALDH) 失活。 东方人与 该基因在面部饮酒后会产生一种综合症 潮红、心动过速和一些恶心。 虽然这种突变常见于 东方人口（约 45%）比例非常低 （约 4%）东方酗酒者。 因此，ALDH 似乎 缺乏可以对酗酒的发展提供一定的免疫力。 据推测，美洲印第安人应该表现出类似的频率 突变，由于蒙古人种的血统。 长期以来，人们一直认为印度人会出现潮红反应。 然而， 这仅记录在 1972 年的一份报告中。 研究人员发现 2-16% 的不同印第安部落的表型 缺乏 ALDH，其他人未能发现任何美洲印第安人患有 ALDH 乙醛脱氢酶缺乏症。 在试点工作中，我们已经确定了一些美洲印第安人 他们自我报告摄入乙醇后出现潮红反应。 因此， 美洲印第安人潮红反应的性质和频率是 不知道。 此外，ALDH活性与 尚未对美洲印第安人的饮酒水平进行研究。 调查美洲印第安人是否存在基因缺陷 在酒精的代谢过程中，我们将： 1) 检查酒精的定性和 对摄入酒精的潮红反应的定量方面 监测皮肤温度、心率、血压、血乙醛 潮红和非潮红美洲印第安人的酒精含量以及 在东方和高加索控制对象中。 2) 确定表型 潮红和非潮红个体的 ALDH 活性水平 三个种族群体。 3）确定美洲印第安人是否有 编码酒精代谢酶的基因发生突变 乙醇脱氢酶 (ADH) 和 ALDH。 4）确定相互关系 潮红反应、ALDH 活性、饮酒率之间 清除率、血液乙醛水平、ADH 和 ALDH 基因型、 饮酒行为的数量/频率和家族史 通过多元统计技术酗酒。 5）在第二个 年份确定各种 ADH 和 ALDH 的群体频率 几个西部印第安部落（黑脚族、苏族、纳瓦霍族）的基因型。 基因型、自我报告的潮红、饮酒之间的关系 将确定酗酒的习惯和家族史。

项目成果

A description of alcohol/drug use and family history of alcoholism among urban American Indians.

对美国城市印第安人酒精/药物使用和酗酒家族史的描述。

• DOI: 10.5820/aian.0801.1997.41
• 发表时间: 1997
• 期刊: American Indian and Alaska native mental health research : journal of the National Center.
• 作者: Gill,K;Elk,ME;Deitrich,RA
• 通讯作者: Deitrich,RA