1998 Fiscal Year Final Research Report Summary
Molecular-Ecogenetic study on the ethiology of alcoholism
| Project/Area Number |
08457126
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Public health/Health science
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| Research Institution | University of Tsukuba |
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Principal Investigator |
HARADA Shoji Institute of Community Medicine, University of Tsukuba Associate Professor, 社会医学系, 助教授 (60086618)
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| Co-Investigator(Kenkyū-buntansha) |
MORITA Nobuaki Institute of Community Medicine, University of Tsukuba Lecturer, 社会医学系, 講師 (10251068)
SATO Shinji Institute of Community Medicine, University of Tsukuba Associate Professor, 社会医学系, 助教授 (90162437)
NOMURA Fumio Institute of Clinical Medicine, University of Tsukuba Associate Professor, 臨床医学系, 助教授 (80164739)
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| Project Period (FY) |
1996 – 1998
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| Keywords | Alcoholism / Genetic risk factor / Case control study / Cholecystokinin B receptor / Serotonin 1A receptor / Mitochondria DNA / Cholecystokinin gene / Genetic polymorphism |
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| Research Abstract |
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.
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