Document Detail


Limited effects of frequent CYP2D6*36-*10 tandem duplication allele on in vivo dextromethorphan metabolism in a Japanese population.
MedLine Citation:
PMID:  20700584     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Kazuma Kiyotani; Makiko Shimizu; Toshio Kumai; Tetsuya Kamataki; Shinichi Kobayashi; Hiroshi Yamazaki
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-08-11
Journal Detail:
Title:  European journal of clinical pharmacology     Volume:  66     ISSN:  1432-1041     ISO Abbreviation:  Eur. J. Clin. Pharmacol.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-16     Completed Date:  2010-11-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1256165     Medline TA:  Eur J Clin Pharmacol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1065-8     Citation Subset:  IM    
Affiliation:
Laboratory for Pharmacogenetics, RIKEN Center for Medicine, Yokohama 230-0045, Japan.
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MeSH Terms
Descriptor/Qualifier:
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:
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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