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Molecular-Ecogenetic study on the ethiology of alcoholism

酒精中毒病因学的分子生态遗传学研究

基本信息

批准号：
08457126
负责人：
HARADA Shoji
金额：
$ 4.99万
依托单位：
University of Tsukuba
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457126/
关键词：
Alcoholism Genetic risk factor Case control study Cholecystokinin B receptor Serotonin 1A receptor Mitochondria DNA Cholecystokinin gene Genetic polymorphism アルコール性肝障害 Aldehyde dehydrogenase Promoter Genetic polymorphism Risk facto

项目摘要

Alcoholism is multifactorial diseases influenced by gene-environmental interaction. Genetic variation of receptor may be associated with alcohol dependance due to its modified function in behavioral and physiological responces. In the present study, polymorphic alleles of cholecystokinin B receptor ( CCKBR), serotonin 1A receptor (HT1AR) , 00K gene and mt-DNA were analyzed. Different mutations were found in the exon of CCKBR and HT1AR.However genotypic distribution of alcoholics was not significantly different with that in controls. Analysis of the mt-DNA showed that a491 bp deletion in the sequence of ATPase exists as heteroplasmy in 58% of alcoholics but not in controls. The heteroplasmic deletion of mt-DNA may be a useful marker for alcohol abuse. Two nticleotide sequence variants were found in CCK gene ; a frequent mutation at nucleotide position -45 Cto T involved in core sequence of Spi binding cis-element of the promoter region, and a C to T substitution at 1662 position in intron 2. Patients with delirium tremens showed significantly higher frequency of the variant compared with the controls (x_24.91 p<0.03). Neuropeptide cholecystokinin (CCK) and the CCK receptors in central nervous system mediate actions on increasing firings, anxiety and nociceptions. These data suggested that the individuals possessing allelic mutation ( -45T ) in the promoter region of 00K gene might be susceptible to delirium tremens caused by alcohol abuse.

酗酒是受基因与环境相互作用影响的多因素疾病。受体的遗传变异可能与酒精依赖有关，因为它在行为和生理反应中的功能发生了改变。本研究对胆囊收缩素B受体(CCKBR)、血清素1A受体(HT1AR)、00K基因和mt-DNA的多态性等位基因进行了分析。 CCKBR和HT1AR外显子存在不同的突变。但酗酒者的基因型分布与对照组没有显着差异。 mt-DNA 分析表明，58% 的酗酒者中 ATPase 序列中存在 491 bp 的异质性缺失，但对照组中则不然。 mt-DNA 的异质性缺失可能是酒精滥用的有用标记。 CCK基因发现两个核苷酸序列变异；启动子区 Spi 结合顺式元件的核心序列 -45 位 C 到 T 的频繁突变，以及内含子 2 中 1662 位点的 C 到 T 替换。与对照相比，震颤性谵妄患者表现出明显更高的变异频率 (x_24.91 p<0.03)。神经肽胆囊收缩素 (CCK) 和中枢神经系统中的 CCK 受体介导增加放电、焦虑和伤害感受的作用。这些数据表明，00K基因启动子区具有等位基因突变（-45T）的个体可能容易患上酒精滥用引起的震颤性谵妄。