Sequence-based analysis of the CYP2D6*36-CYP2D6*10 tandem-type arrangement, a major CYP2D6*10 haplotype in the Japanese population

Drug Metab Pharmacokinet. 2006 Jun;21(3):208-16. doi: 10.2133/dmpk.21.208.

Abstract

The frequency of the CYP2D6*10 allele (100C>T) in the Japanese is relatively high (0.3-0.4), and the two *10-related genes, Ch1 (currently *10B) and Ch2 (*36), and their tandem arrangement Ch(2)-Ch(1) (*36-*10B) have been reported. Although the tandem form of *36-*10 is assumed to be a major form, no detailed information has been reported for its intervening and flanking regions. Thus in this study, the tandem-type *36-*10B and the single-type *10 were analyzed by long-range PCR and sequencing of the subsequent nested PCR products. The sequence of the entire *36-*10 region confirmed the recombination of CYP2D6*10 with CYP2D7P. Also, we found that most of the *10B-harboring haplotypes have the upstream *36 gene and that the majority of the remaining haplotypes are the single-type *10B. Haplotype frequencies of the single-type *10 and *36-*10B were 0.06 and 0.30, respectively, in the subjects analyzed. Additionally, several novel single nucleotide polymorphisms (SNPs) were found in the *36 region and several *36 haplotypes were identified. This sequence information is an important addition to the CYP2D6 sequence data that was obtained by the human genome project.

MeSH terms

  • 3' Flanking Region / genetics
  • 5' Flanking Region / genetics
  • Asian People / genetics*
  • Cytochrome P-450 CYP2D6 / genetics*
  • Gene Frequency
  • Gene Order
  • Haplotypes / genetics*
  • Humans
  • Isoenzymes / genetics
  • Japan
  • Molecular Sequence Data
  • Polymerase Chain Reaction / methods
  • Polymorphism, Single Nucleotide / genetics
  • Sequence Analysis, Protein / methods*

Substances

  • Isoenzymes
  • Cytochrome P-450 CYP2D6

Associated data

  • GENBANK/DQ211353
  • GENBANK/DQ211354
  • GENBANK/DQ211355