title: Limited effects of frequent CYP2D6*36-*10 tandem duplication allele on in vivo dextromethorphan metabolism in a Japanese population.
abstract: OBJECTIVE
  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.affiliation: Laboratory for Pharmacogenetics, RIKEN Center for Medicine, Yokohama 230-0045, Japan.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Kiyotani
authors.forename: Makiko
authors.initials: M
authors.lastname: Shimizu
authors.forename: Toshio
authors.initials: T
authors.lastname: Kumai
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kamataki
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamazaki
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism*; D003915:Dextromethorphan / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D010641:Phenotype; D012016:Reference Values
chemical_list: D018691:Excitatory Amino Acid Antagonists; D003915:Dextromethorphan; D019389:Cytochrome P-450 CYP2D6