2000 Fiscal Year Final Research Report Summary
GENETIC POLYMORPHISM OF DRUG METABOLIZING-ENZYME ; ANALYSIS OF NOVEL POLYMORPHISM AND DEVELOPMENT OF GENOTYPING METHOD
| Project/Area Number |
10557242
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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 | 展開研究 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
ARIYOSHI Noritaka Hokkaido Univ., Asso.Prof., 大学院・薬学研究科, 助教授 (00243957)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAYAMA Kazuo Hokkaido Univ., Inst., 大学院・薬学研究科, 助手 (20261323)
TAKAHASHI Yoshiki Hokkaido Univ., Inst., 大学院・薬学研究科, 助手 (80292019)
FUJITA Ken-ichi Hokkaido Univ., Inst., 大学院・薬学研究科, 助手 (60281820)
MINE Tsuyoshi Sumitomo Pharm., Senior Investigator, 主任研究員
KAMATAKI Tetsuya Hokkaido Univ., Prof., 大学院・薬学研究科, 教授 (00009177)
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| Project Period (FY) |
1998 – 2000
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| Keywords | drug metabolism / cytochrome P450 / genetic polymorphism / CYP2D6 / Adverse reaction / poor metabolizer / gene analysis / CYP2D6^*36 |
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| Research Abstract |
CYP2D6 is a form of cytochrome P450(CYP)involved in the metabolism of more than 40 clinically important drugs including some tricyclic antidepressants, antiarrhythmics, b-adrenergic blockers and histamin H_1 antagonists. This form of CYP is polymorphically expressed in a population and characterized as two phenotypes, extensive metabolizers and poor metabolizers(PM). It was assumed that there may be some unknown polymorphisms in Orientals, because major variants in Caucasians could not fully account for the frequency of the PM in Japanese. Analysis of the CYP2D6 gene in two Japanese PMs identified by phenotyping using debrisoquine was performed. As a result, novel two mutations were discovered. was one-base insertion in exon 5, leading to generation a stop codon at 11 dp downstream. This variant was designated as the CYP2D6^*21. The other one was tandem repeat of inactive gene, CYP2D6^*36, at regions of the CYP2D locus. Genotyping method was established against each of the variant allele. The frequency of the CYP2D6^*36-^*36 could not be determined in this study due to small sise of subjects. On the other hand, the CYP2D6^*21 appeared to be one of the major variant causing PM phenotype in Japanese.
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