2000 Fiscal Year Final Research Report Summary
Genetic variations of promoter sequences of aldehyde dehydrogenase and individual differences of alcohol metabolism
| Project/Area Number |
11670412
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Legal medicine
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| Research Institution | Mie University |
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Principal Investigator |
FUKUNAGA Tatsushige Mie University Faculty of Medicine, Professor, 医学部, 教授 (70156800)
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| Co-Investigator(Kenkyū-buntansha) |
SAIJOH Kiyofumi Kanazawa Univ.Faculty of Med., Professor, 医学部, 教授 (00178469)
YAMAMOTO Hidetaka Mie Univ.Faculty of.Med., Assistant, 医学部, 助手 (90158296)
TANEGASHIMA Akio Mie Univ.Faculty of Med.Lecturer, 医学部, 講師 (70283520)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Alcohol, ethyl / Acetaldehyde / ALDH / cDNA / mRNA / Differential display / Promoter / Polymorphism |
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| Research Abstract |
To elucidate the individual differences of alcohol metabolism and effects, the promoter regions were analyzed in the present study. To isolate differentially expressed genes in the nucleus accumbens (NA) from chronically ethanol-administered rats may help understand underlying molecular mechanisms for development and reinforcement of ethanol addiction. According to differential display around 0.1% of mRNA was considered to be affected by chronic ethanol-administration in the NA, regardless whether ethanol directly affected gene expression in the NA or gene alteration was secondary to alteration in neuronal activity by ethanol. Among them, 46 clones successfully re-amplified were screened by reverse Northern blot analysis and 8 up-regulated and 7 down-regulated genes were isolated. One of the up-regulated cDNA was homologous to human TGFβ1-and its preferential expression was also observed in the cerebellum and LC.Since clone c10 displayed extremely preferential expression in the ethanol-administered NA, its upstream sequence was analyzed by 5'RACE but the coding sequence was not yet isolated. c118 was enriched in the ethanol-administered NA and displayed high homology to mouse KH domain RNA binding protein QKI-5A.The 5'RACE analysis confirmed that this clone encoded rat QKI-5A.Since QKI proteins are considered to be regulators of myelination and their absence causes dysmyelination, its up-regulation may play a protect role against ethanol-induced dysmyelination. Other 12 cDNAs were registered as ESTs or novel so that their functions were unknown. It seems important to identify their upstream sequences including coding regions and promoter sequences not only to estimate the roles in ethanol addiction of these differentially expressed genes but also to clarify whether ethanol-dependent gene-regulation exists or not.
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