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展中起作用 酒精中毒。 拟议的研究将检查一些遗传 美洲印第安人人口的酒精中毒。 虽然主要 旨在确定与之相关的基因的研究计划 酗酒已经开始于高加索人口，这些研究在很大程度上很大程度上 排除印度人民。 在东方人中，已经确定了单个基因突变，该突变降低了 酒精摄入。 突变是单个基对替代 使酶醛脱氢酶（ALDH）无活性。 东方 该基因在饮酒后患有综合征 潮红，心动过速和一些恶心。 而突变很常见 东方人口（约45％）的比例很低 （约4％）东方酒精中毒。 因此，似乎Aldh 不足为酒精中毒的发展提供了一些免疫力。 假定美国印第安人应该显示出类似的频率 突变，由于蒙古种族的血统。 长期以来，印第安人的冲洗反应一直被认为是发生的。 然而， 这仅在1972年的一份报告中记录在一份报告中。虽然有些 研究人员在表型上发现了2-16％的印度部落 缺乏ALDH，其他人未能找到任何美国印第安人 ALDH缺乏。 在飞行员工作中，我们确定了一些美国印第安人 在摄入乙醇后，自我报告的冲洗反应。 因此， 美洲印第安人的潮红反应的性质和频率是 不知道。 另外，ALDH活动与 在美洲印第安人尚未研究饮酒水平。 调查美国印第安人有遗传缺陷的可能性 在酒精的代谢中：1）检查定性和 冲洗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，血液乙醛 以及潮红和非燃烧的美洲印第安人的酒精水平以及 在东方和高加索控制受试者中。 2）确定表型 来自潮红和非冲洗个体的ALDH活动水平 三个种族群体。 3）确定美国印第安人是否有 基因的突变，这些基因代码为酒精代谢酶 酒精脱氢酶（ADH）和ALDH。 4）确定相互关系 在冲洗响应，ALDH活性，酒精速率之间 清除，血液乙醛水平，ADH和ALDH的基因型， 饮酒行为的数量/频率 通过多元统计技术酗酒。 5）第二 年确定各种ADH和ALDH的人口频率 几个西印度部落（Blackfeet，Sioux，Navaho）的基因型。 基因型，自我报告的冲洗，饮酒之间的关系 将确定酒精中毒的实践和家族史。

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