ALCOHOL PHARMACOGENETICS IN MEXICAN AMERICANS

墨西哥裔美国人的酒精药物遗传学

• 批准号: 7376092
• 负责人: MICHAEL SMITH
• 金额: $ 11.03万
• 依托单位: LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7376092
• 关键词: ALCOHOL; PHARMACOGENETICS; MEXICAN; AMERICANS

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The primary focus of the proposed project is to identify the genetic risk factors for alcoholism in Mexican Americans. The genes selected for this study belong to two major categories: (1) those controlling how alcohol is broken down and eliminated from the body and (2) those associated with the action of alcohol and/or the potential for addiction to alcohol (ie. dopamine, serotonin and GABA ). As the risk factors involved in alcohol use and addiction are most likely due to a number of different reasons, this appears to be a reasonable approach. With the simultaneous examination of genes from both categories, we aim at not only describing the distribution in Mexican Americans of genes that have been well characterized in other populations and found to be associated with drinking behavior, alcohol addiction and alcohol related medical problems, but also to explore the interaction of those two categories of genes in alcoholism. Furthermore, it is crucial to include women because of the serious drinking problem in female Mexican Americans and because women are more susceptible to alcohol related injury. Although we do not anticipate that the frequency of a certain gene is different between men and women in the non-alcoholic population, we do speculate that a stronger association between genetics and alcoholism might be found in women than men if both genders have the same severity of alcoholism, since female gender is a protecting factor for drinking. Therefore, the central theme of this application is to identify the genetic risk factors for alcoholism in Mexican Americans. We will address how these genetic factors are interrelated, how smoking modulate genetic factors for alcoholism, and how gender affects genetic association. As mentioned above, besides alcoholism, the data collected would also allow us to address other aspects of alcohol related problem including ethnic variation, alcohol drinking behavior and pattern, clinical profile and potentially alcoholic liver disease. The proposed study includes 1200 subjects, divided into two groups: an alcoholic group and a non-alcoholic group, with each group comprising equal numbers of males and females (n = 300 each. Only those with homogeneous Mexican American backgrounds will be included in the study, this is defined as having 3 out 4 grandparents who are of Mexican heritage. After obtaining informed consent, potential subjects will be screened using a brief screening form to elicit information to establish their eligibility for the study. These will include information on demographics (e.g., ethnicity, gender and age), alcohol drinking habits, and usage of cigarettes and other substances of addictive potential, psychiatric and medical history. Subjects passing the screening will be invited for the initial assessment. Detailed medical and psychiatric history, including the use and abuse of alcohol and other substances, will be obtained. Alcoholic subjects will also be interviewed using several instruments and will also have blood drawn for genetic studies. The instruments to be used during the interview include questionnaires to assess the physical, psychosocial and psychiatric manifestations of alcohol abuse and dependence and related psychiatric disorders (The Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA-II), and a self administered questionnaire to assess the severity of different aspects of alcohol addiction (Severity of Alcohol Dependence Questionnaire (SADQ). Physical examination and laboratory tests (complete blood counts, chemistry panel, liver function tests, serum antinuclear antibody, hepatitis C antibody, hepatitis B surface antigen, urine analysis and urine toxicology screen) will then be performed. During this session, a total of 70 ml of blood will be obtained from each subject. Ten ml of blood will be used for DNA extraction and genotyping. Another twenty ml of blood will be collected for storage as backup for additional DNA extraction. Blood and urine tests will be done in our NIH funded General Clinical Research Center (GCRC).

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。拟议项目的主要重点是确定墨西哥裔美国人酗酒的遗传风险因素。为这项研究选择的基因分为两大类：(1)那些控制酒精如何被分解和从体内消除的基因和(2)与酒精的作用和/或对酒精上瘾的可能性有关的基因(即。多巴胺、5-羟色胺和GABA)。由于酒精使用和成瘾涉及的风险因素很可能是由许多不同的原因造成的，这似乎是一个合理的方法。通过同时检测这两个类别的基因，我们的目标不仅是描述在墨西哥裔美国人中的分布，这些基因在其他人群中已经被很好地描述，并被发现与饮酒行为、酒精成瘾和与酒精相关的医疗问题有关，而且还旨在探索这两个类别的基因在酒精中毒中的相互作用。此外，将女性包括在内至关重要，因为墨西哥裔美国女性饮酒问题严重，而且女性更容易受到与酒精有关的伤害。尽管我们预计在非酗酒人群中，某个基因的频率不会在男性和女性之间有所不同，但我们确实推测，如果女性和男性的酒精中毒程度相同，那么基因和酒精中毒之间的联系可能会比男性更强，因为女性是饮酒的保护因素。因此，该应用程序的中心主题是确定墨西哥裔美国人酗酒的遗传风险因素。我们将讨论这些遗传因素是如何相互关联的，吸烟如何调节酒精中毒的遗传因素，以及性别如何影响遗传关联。如上所述，除了酗酒外，收集的数据还将使我们能够解决与酒精有关的问题的其他方面，包括种族差异、饮酒行为和模式、临床特征以及潜在的酒精性肝病。这项拟议的研究包括1200名受试者，分为两组：酗酒组和非酗酒组，每组包括同等数量的男性和女性(n=300)。只有具有相同墨西哥裔美国人背景的人才会被纳入这项研究，这被定义为四分之三的祖父母都有墨西哥血统。在获得知情同意后，将使用简短的筛选表格对潜在受试者进行筛选，以获取信息以确定他们是否符合研究的资格。这些资料将包括人口统计资料(例如，种族、性别和年龄)、饮酒习惯、香烟和其他可能使人上瘾的物质的使用情况、精神病史和病史。通过筛选的受试者将被邀请参加初步评估。将获得详细的医疗和精神病史，包括酒精和其他物质的使用和滥用。酗酒的受试者还将使用几种工具接受采访，并将为遗传学研究抽血。访谈期间使用的工具包括评估酒精滥用和依赖的身体、心理、社会和精神表现以及相关精神障碍的问卷(酒精中毒遗传学半结构评估(SSAGA-II))，以及评估酒精成瘾不同方面严重程度的自填式问卷(酒精依赖严重程度问卷(SADQ))。然后进行体格检查和实验室检查(完整的血细胞计数、化学成分、肝功能测试、血清抗核抗体、丙型肝炎抗体、乙肝表面抗原、尿液分析和尿毒学筛查)。在这次会议期间，每个受试者总共将获得70毫升的血液。10毫升的血液将用于DNA提取和基因分型。另外20毫升的血液将被收集起来储存，作为进一步提取DNA的备份。血液和尿液测试将在我们由NIH资助的普通临床研究中心(GCRC)进行。