| Limited effects of frequent CYP2D6*36-*10 tandem duplication allele on in vivo dextromethorphan metabolism in a Japanese population. | |
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MedLine Citation:
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PMID: 20700584 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: although CYP2D6*36 was thought to be one of the alleles causing the poor metabolizer phenotype, several in vitro studies clarified that the enzyme produced by CYP2D6*36 showed enzymatic activities. However, the effects of CYP2D6*36 in tandem with CYP2D6*10 on the in vivo CYP2D6 activity have been unclear. In this study, we investigated in vivo metabolic capacities of CYP2D6 among the subjects carrying different numbers of CYP2D6*36 in tandem with CYP2D6*10. METHODS: we measured the metabolic ratio (MR) of dextromethorphan in 98 subjects. We determined the CYP2D6 genotype of these subjects, including allelic copy number of CYP2D6*10 and CYP2D6*36 by direct sequencing, TaqMan assay, and real-time Invader assay. RESULTS: single copies of CYP2D6*10 and tandem duplication of CYP2D6*36-*10 alleles were found at frequencies of 8.7 and 32.7%, respectively. Median dextromethorphan MRs of the subjects carrying CYP2D6*10 and CYP2D6*36-*10 were not significantly different (P = 0.24). CONCLUSIONS: CYP2D6*36 in tandem with CYP2D6*10 plays a minor role in interindividual variation of dextromethorphan metabolism in vivo. |
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Authors:
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Kazuma Kiyotani; Makiko Shimizu; Toshio Kumai; Tetsuya Kamataki; Shinichi Kobayashi; Hiroshi Yamazaki |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-08-11 |
Journal Detail:
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Title: European journal of clinical pharmacology Volume: 66 ISSN: 1432-1041 ISO Abbreviation: Eur. J. Clin. Pharmacol. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-09-16 Completed Date: 2010-11-22 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1256165 Medline TA: Eur J Clin Pharmacol Country: Germany |
Other Details:
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Languages: eng Pagination: 1065-8 Citation Subset: IM |
Affiliation:
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Laboratory for Pharmacogenetics, RIKEN Center for Medicine, Yokohama 230-0045, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Asian Continental Ancestry Group / genetics* Cytochrome P-450 CYP2D6 / genetics*, metabolism* Dextromethorphan / metabolism* Excitatory Amino Acid Antagonists / metabolism Gene Frequency* Genotype Humans Japan Male Phenotype Reference Values |
| Chemical | |
Reg. No./Substance:
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0/Excitatory Amino Acid Antagonists; 125-71-3/Dextromethorphan; EC 1.14.14.1/Cytochrome P-450 CYP2D6 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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