HUMAN ALCOHOL DEHYDROGENASE & ALDEHYDE DEHYDROGENASE

人体酒精脱氢酶

• 批准号: 3109062
• 负责人: AKIRA Y YOSHIDA
• 金额: $ 29.48万
• 依托单位: BECKMAN RES INST OF THE CITY OF HOPE
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-04-01 至 1994-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3109062
• 关键词: Asians; Native Americans; acetaldehyde; alcohol dehydrogenase; alcoholic beverage consumption; alcoholism /alcohol abuse; aldehyde dehydrogenases; alleles; biological polymorphism; chromatography; complementary DNA; cytogenetics; developmental genetics; drug tolerance; ethanol; gene expression; gene mutation; genetic library; genetic manipulation; genetic mapping; genome; genotype; human population genetics; human tissue; isozymes; mass spectrometry; molecular cloning; nucleic acid hybridization; nucleic acid probes; radionuclides; structural genes; ultracentrifugation

The Class I alcohol dehydrogenases (ADH) and the cytosolic and mitochondrial aldehyde dehydrogenases (ALDHl and ALDH2) play major roles in ethanol and acetaldehyde oxidation. The genetic variations of these enzymes would affect the clearance of the toxic chemicals and alcohol intoxication, and indirectly affect the development of alcohol-related diseases. The racial differences in the incidence of alcohol sensitivity and alcoholism may be, in Part, attributed to the genetic background. The overall objectives of the Project are: to elucidate the genomic structures and gene expressions of ADH and ALDH; to examine their genetic variations and identify their mutation sites, and to elucidate the correlations of these genetic variations to alcoholic-related problems. The following projects will be undertaken: 1) Determination of the genomic structure of ADH cluster locus, which includes three genes, i.e. ADH, (for alpha-subunit), ADH1 (for beta-subunit), and ADH1 (for gamma-subunit), their 3'- and 5'- regions, and possibly pseudogene(s); 2) Study of developmental regulation of expression of the cytosolic ALDH1 and the mitochondrial ALDH2 loci, by analyzing translation products and quantity and quality of primary transcripts and mRNAs in fetal and adult livers; 3) Determination of the genotypes of ADH2 and ALDH2 loci in subjects with alcoholic diseases and control subjects in Caucasians, Orientals (Japanese and Koreans) and American Indians, and examination of restriction fragment length polymorphism of the loci in these populations; and 4) Exploration and characterization of the cytosolic ALDHl variants related to alcohol sensitivity and other alcoholic problems.

I 类乙醇脱氢酶 (ADH) 和胞质和 线粒体醛脱氢酶（ALDH1 和 ALDH2）起主要作用 乙醇和乙醛氧化中的作用。 遗传性 这些酶的变化会影响 有毒化学品和酒精中毒，并间接影响 与酒精有关的疾病的发展。 种族 酒精敏感性和酒精中毒发生率的差异 可能部分归因于遗传背景。 该项目的总体目标是： 阐明基因组 ADH 和 ALDH 的结构和基因表达；检查他们的 遗传变异并识别其突变位点，并 阐明这些遗传变异与 与酒精相关的问题。 将开展以下项目： 1) 确定 ADH簇位点的基因组结构，包括三个 基因，即 ADH（对于 α 亚基）、ADH1（对于 β 亚基）、 和 ADH1（伽马亚基），其 3'- 和 5'- 区域，以及 可能是假基因； 2）发育调控研究 胞质 ALDH1 和线粒体 ALDH2 的表达 loci，通过分析翻译产品以及数量和质量 胎儿和成人肝脏中的初级转录物和 mRNA； 3） 受试者 ADH2 和 ALDH2 基因座基因型的测定 患有酒精疾病的白种人和对照受试者， 东方人（日本人和韩国人）和美洲印第安人，以及 限制性片段长度多态性检查 这些人群中的基因座； 4) 探索和表征 与酒精敏感性相关的胞质 ALDH1 变体和 其他酒精问题。