ALCOHOL PHARMACOGENETICS IN MEXICAN AMERICANS

这个子项目是众多研究子项目之一

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 homogenous 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).