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Epidemiological study on isozyme variants of aldehyde dehydrogenase and alcoholism.

乙醛脱氢酶同工酶变异体与酒精中毒的流行病学研究。

基本信息

批准号：
63570501
负责人：
HARADA Shoji
金额：
$ 1.09万
依托单位：
University of Tsukuba
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1989
项目状态：
已结题

项目摘要

1) POLYMORPHISM OF ALDEHYDE DEHYDROGENASE IN HUMAN SALIVA A new ALDH isozyme was found in human saliva showing different isozyme pattern other than ALDH I, II, III, IV reported previously. Biochemical characterization concerning pI, Km values and molecular weight of the subunit for saliva AIDH in the tissues. A specific antiserum against saliva AIDH made no precipitate to ALDH I, II, III and IV. To confirm the possible existence of a new locus coding the allele of ALDH V, a total of 15 monozygotic twin families were investigated to determine the saliva ALDH V phenotypes. This data supported that at least two alleles classified as ALDH normal and deficient exist to determine the ALDH V phenotypes. The present data with alcoholics indicated that a higher frequency (87.4%) of ALDH V normal and a lower frequency (12.6%) of ALDH deficiency were found than those of healthy controls (P<0.01). This finding may support that saliva ALDH is a possible genetic marker of alcohol abuse.2) GENOTYPES OF MITOCHONDRIAL ALDEHYDE DEHYDROGENASE AND ACETALDEME METABOLISM. The genotypes of mitochondrial aldehyde dehydrogenase (ALDH_2) locus were determined using advanced technique for DNA analysis in 41 healthy Japanese and their acetaldehyde metabolism after alcohol intake was investigated using gaschromatograph. Moreover, the gene frequency of ALDH^1_ and ALDH^2_ were compared between 41 healthy controls and 50 Japanese alcoholics. Different concentration of blood acetaldehyde after alcohol intake (1 ml whiskey/kg. body weight) were found among the three genotypes of ALDH_2 from healthy controls. The homozygous genotype of ALDH^1_ showed the lowest concentration (4.9<plus-minus>1.7muM). The subjects showing heterozygous genotype of ALDH^1_ and ALDH^2_ had lower concentration (24.6<plus-minus>8.4muM) than that of homo zygous genotype of ALDH^2_ (71.2<plus-minus>32.3muM). The gene frequency of ALDH^2_ in alcoholics was significantly lower than that of healthy controls (P<0.01).

1) 人类唾液中乙醛脱氢酶的多态性在人类唾液中发现了一种新的 ALDH 同工酶，其同工酶模式与之前报道的 ALDH I、II、III、IV 不同。关于组织中唾液 AIDH 亚基的 pI、Km 值和分子量的生化特征。抗唾液 AIDH 的特异性抗血清不会沉淀 ALDH I、II、III 和 IV。为了确认编码 ALDH V 等位基因的新基因座的可能存在，总共研究了 15 个同卵双胞胎家族以确定唾液 ALDH V 表型。该数据支持至少存在两个分类为 ALDH 正常和缺陷的等位基因以确定 ALDH V 表型。目前酗酒者的数据表明，与健康对照相比，ALDH V 正常的频率较高（87.4%），ALDH 缺乏的频率较低（12.6%）（P<0.01）。这一发现可能支持唾液 ALDH 可能是酒精滥用的遗传标记。2) 线粒体醛脱氢酶和乙缩醛代谢的基因型。利用先进的 DNA 分析技术确定了 41 名健康日本人的线粒体醛脱氢酶 (ALDH_2) 基因座的基因型，并使用气相色谱仪研究了他们饮酒后的乙醛代谢。此外，还比较了 41 名健康对照者和 50 名日本酗酒者的 ALDH^1_ 和 ALDH^2_ 基因频率。健康对照者的三种ALDH_2基因型中发现饮酒后血液乙醛浓度不同（1毫升威士忌/公斤体重）。 ALDH^1_纯合基因型的浓度最低(4.9±1.7μM)。显示ALDH^1_和ALDH^2_杂合基因型的受试者的浓度(24.6±8.4μM)低于ALDH^2_纯合基因型(71.2±32.3μM)。酗酒者的ALDH^2_基因频率显着低于健康对照者（P<0.01）。