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

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）：西班牙裔是美国增长最快的族裔群体之一，截至 2000 年 3 月，其人口占全国人口的 12%，与其他族裔背景（例如白人和非裔美国人）相比，他们患有酒精相关问题的比例更高。尽管如此，人们对可能导致此类风险的遗传因素仍知之甚少。在已建立的研究基础设施的基础上，这项竞争性的延续申请将系统地探索和检查墨西哥裔美国人酗酒的遗传机制。这项正在进行的研究计划已开始确定独特的遗传模式，这些模式可能是导致该人群酗酒和酒精相关健康问题风险增加的部分原因。其中包括 (1) ALDH2*2（乙醛脱氢酶）和 ADH2*2（乙醇脱氢酶）的等位基因频率极低； (2) ADH3*2和CYP2E1 c2（细胞色素P4502E1）等位基因比例较高； (3)ADH3*2、ADH2*1、DRD2(多巴胺受体-141C Del/Ins)和5-羟色胺转运蛋白基因连锁多态区(5-HTTLPR)与酗酒的关联； (4) ADH3*2 和 ADH2*1 等位基因与酗酒有很强的相关性； (5) DRD2 Taq1 A 和 1B 等位基因与饮酒年龄过早的关系。在这个新的融资周期中，我们计划进一步探讨和阐明这些发现的含义。具体来说，我们将（1）扩大我们的研究范围，将有酗酒问题的墨西哥裔美国女性纳入其中； (2) 进一步研究这些多态性的作用及其潜在的相互作用，与墨西哥裔美国人酗酒的风险相关； (3) 检查这些风险与酗酒严重程度（即酗酒和过早饮酒）之间的关系； (4) 表征并确定与墨西哥裔美国人饮酒相关的 DRD2 单倍型，并评估单倍型与等位基因分析在描述导致酗酒的危险因素方面的相对优势。这项研究将首次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。这项研究的结果不仅应该有助于更好地了解墨西哥裔美国人的酒精使用和滥用，而且还有助于建立关于酒精药物遗传学的种族差异和可能导致该少数群体酗酒率高的机制的知识库。

项目成果

Polymorphisms of CYP2C19 and CYP2D6 in Israeli ethnic groups.

• DOI: 10.2165/00129785-200404060-00006
• 发表时间: 2004-01-01
• 期刊: American journal of pharmacogenomics : genomics-related research in drug development and clinical practice
• 作者: Luo, Huai-Rong;Aloumanis, Vasileios;Wan, Yu-Jui Yvonne
• 通讯作者: Wan, Yu-Jui Yvonne

Nur-related receptor 1 gene polymorphisms and alcohol dependence in Mexican Americans.

• DOI: 10.3748/wjg.v18.i37.5276
• 发表时间: 2012-10
• 期刊: World journal of gastroenterology
• 影响因子: 4.3
• 作者: Yaming Wei;Yanlei Du;Y. Nie;Yu-yuan Li;Y. Wan

Linkage disequilibrium blocks, haplotype structure, and htSNPs of human CYP7A1 gene.

人CYP7A1基因的连锁不平衡块，单倍型结构和HTSNP。

• DOI: 10.1186/1471-2156-7-29
• 发表时间: 2006-05-18
• 期刊: BMC GENETICS
• 影响因子: 2.9
• 作者: Nakamoto, Kaori;Wang, Shuang;Jenison, Robert D.;Guo, Grace L.;Klaassen, Curtis D.;Wan, Yu-Jui Yvonne;Zhong, Xiao-bo
• 通讯作者: Zhong, Xiao-bo

The association of exon 3 VNTR polymorphism of the dopamine receptor D4 (DRD4) gene with alcoholism in Mexican Americans.

• DOI: 10.1016/j.psychres.2010.02.021
• 发表时间: 2010-05-30
• 期刊: PSYCHIATRY RESEARCH
• 影响因子: 11.3
• 作者: Du, Yanlei;Yang, Min;Yeh, Hung-Wen;Wan, Yu-Jui Yvonne
• 通讯作者: Wan, Yu-Jui Yvonne

Identification of CYP2D6 impaired functional alleles in Mexican Americans.

墨西哥裔美国人中 CYP2D6 功能受损等位基因的鉴定。

• DOI: 10.1007/s00228-005-0044-4
• 发表时间: 2005
• 期刊: European journal of clinical pharmacology
• 影响因子: 2.9
• 作者: Luo,Huai-Rong;Gaedigk,Andrea;Aloumanis,Vasileios;Wan,Yu-JuiYvonne
• 通讯作者: Wan,Yu-JuiYvonne