Alcohol Pharmacogenetics in Mexican Americans

墨西哥裔美国人的酒精药物遗传学

• 批准号: 7854437
• 负责人: Yu-Jui Yvonne Wan
• 金额: $ 8.05万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7854437
• 关键词: AODR mortality; Accounting; Addictive Behavior; African American; Age of Onset; Alcohol abuse; Alcohol consumption; Alcohol dehydrogenase; Alcohol dependence; Alcoholic beverage heavy drinker; Alcoholism; Alcohols; Alleles; Behavior; Behavioral; CYP2E1 gene; Caucasians; Caucasoid Race; Censuses; Clinical; Cytochromes c2; DRD2 gene; Data; Development; Dopamine Receptor; Emotional; Ethanol Metabolism; Ethnic group; Funding; Gene Frequency; Genes; Genetic; Genetic Polymorphism; Genotype; Grant; Haplotypes; Health; Heavy Drinking; Hispanics; Knowledge; Link; Methods; Mexican; Mexican Americans; Minority; Minority Groups; Morbidity - disease rate; Pattern; Pharmacogenetics; Population; Relative (related person); Research; Research Infrastructure; Research Personnel; Risk; Risk Factors; Role; Severities; Smoker; Smoking; Structure; Testing; Time; United States; Variant; Woman; addiction; alcohol related problem; aldehyde dehydrogenases; binge drinking; clinical phenotype; drinking; early onset; ethnic difference; ethnic minority population; experience; genetic association; genetic profiling; genetic risk factor; high risk; knowledge base; male; men; non-alcoholic; problem drinker; programs; serotonin transporter; AODR mortality; Accounting; Addictive Behavior; African American; Age of Onset; Alcohol abuse; Alcohol consumption; Alcohol dehydrogenase; Alcohol dependence; Alcoholic beverage heavy drinker; Alcoholism; Alcohols; Alleles; Behavior; Behavioral; CYP2E1 gene; Caucasians; Caucasoid Race; Censuses; Clinical; Cytochromes c2; DRD2 gene; Data; Development; Dopamine Receptor; Emotional; Ethanol Metabolism; Ethnic group; Funding; Gene Frequency; Genes; Genetic; Genetic Polymorphism; Genotype; Grant; Haplotypes; Health; Heavy Drinking; Hispanics; Knowledge; Link; Methods; Mexican; Mexican Americans; Minority; Minority Groups; Morbidity - disease rate; Pattern; Pharmacogenetics; Population; Relative (related person); Research; Research Infrastructure; Research Personnel; Risk; Risk Factors; Role; Severities; Smoker; Smoking; Structure; Testing; Time; United States; Variant; Woman; addiction; alcohol related problem; aldehyde dehydrogenases; binge drinking; clinical phenotype; drinking; early onset; ethnic difference; ethnic minority population; experience; genetic association; genetic profiling; genetic risk factor; high risk; knowledge base; male; men; non-alcoholic; problem drinker; programs; serotonin transporter

DESCRIPTION (provided by applicant): Representing one of the fastest growing ethnic groups in the United States, Hispanics accounted for 12% of the nation's population by March 2000, and suffer from higher rates of alcohol related problems as compared with those from other ethnic backgrounds (e.g., Caucasians and African Americans). This notwithstanding, genetic factors that might contribute to such risks remain poorly understood. Building upon the research infrastructure that has been established, this competitive continuation application will systematically explore and examine genetic mechanisms for alcoholism in Mexican Americans. This ongoing research program has started to identify unique genetic patterns that might be in part responsible for the heightened risk for alcoholism and alcohol associated health problems in this population. These include (1) extremely low allele frequency for both ALDH2*2 (aldehyde dehydrogenase) and ADH2*2 (alcohol dehydrogenase); (2) a relatively high rate of ADH3*2 and CYP2E1 c2 (cytochrome P4502E1) alleles; (3) association of ADH3*2, ADH2*1, DRD2 (dopamine receptor -141C Del/Ins) and serotonin transporter gene-linked polymorphic region (5-HTTLPR) with alcoholism; (4) a strong association of ADH3*2 and ADH2*1 alleles with binge drinking; and (5) association of the DRD2 Taq1 A and 1B alleles with early age of onset for drinking. In this new funding cycle, we plan to further pursue and clarify the meaning of these findings. Specifically, we will (1) expand our study to include Mexican American women with alcohol problems; (2) further examine the role of these polymorphisms, as well as their potential interactions, in relation to risks for alcoholism in Mexican American populations; (3) examine the role of these risks in relationship with the severity of alcoholism i.e. binge drinking and early onset of drinking; (4) characterize and determine the haplotype of DRD2 in association with drinking in Mexican Americans, and assess the relative advantage of haplotype vs. allelic analysis in delineating risk factors contributory to the development of alcoholism. This study will be the first to systematically examine how genetic factors modulate alcohol dependence and abuse in Mexican Americans. Results derived from such a study should not only provide for a better understanding of alcohol use and abuse among Mexican Americans, but also contribute towards a knowledge base regarding ethnic differences in alcohol pharmacogenetics and mechanisms that might be responsible for the high rate of alcoholism in this minority population.

描述（由申请人提供）：代表美国增长最快的族裔之一，到2000年3月，西班牙裔占该国人口的12％，与其他种族背景相比，与酒精相关的问题较高（例如，高加索人和非裔美国人）。尽管如此，可能导致这种风险的遗传因素仍然对此知之甚少。在建立的研究基础设施的基础上，这种竞争性的延续应用将系统地探索和检查墨西哥裔美国人酒精中毒的遗传机制。这项正在进行的研究计划已开始确定独特的遗传模式，这可能是导致该人群中酒精中毒和与酒精相关的健康问题的风险增加的原因。其中包括（1）ALDH2*2（醛脱氢酶）和ADH2*2（酒精脱氢酶）的极低等位基因频率； （2）相对较高的ADH3*2和CYP2E1 C2（细胞色素P4502E1）等位基因的速率； （3）ADH3*2，ADH2*1，DRD2（多巴胺受体-141C DEL/INS）和5-羟色胺转运蛋白转运蛋白基因链接多态性区域（5-HTTLPR）与酒精中毒的关联； （4）ADH3*2和ADH2*1等位基因与暴饮暴食的牢固关联； （5）DRD2 TAQ1 A和1B等位基因的关联与饮酒的初期。在这个新的资金周期中，我们计划进一步追求并阐明这些发现的含义。具体来说，我们将（1）扩展我们的研究以包括墨西哥裔美国妇女饮酒问题； （2）进一步研究了这些多态性的作用及其潜在的相互作用，与墨西哥裔美国人的酒精中毒风险有关； （3）检查这些风险与酒精中毒的严重程度，即暴饮暴食和早期饮酒的作用； （4）表征并确定DRD2的单倍型与墨西哥裔美国人的饮酒相关，并评估单倍型与等位基因分析在描述危险因素中的相对优势有助于酗酒的发展。这项研究将是第一个系统地研究遗传因素如何调节墨西哥裔美国人的酒精依赖和滥用的一项研究。从这项研究中得出的结果不仅应提供对墨西哥裔美国人中酒精使用和滥用的更好理解，而且还有助于有关酒精药遗传学和机制的种族差异的知识基础，这些机制可能导致了这一少数人口中的酗酒率很高。