Diverse structures of chimeric CYP-REP7/6-containing CYP2D6 and a novel defective CYP2D6 haplotype harboring single-type *36 and CYP-REP7/6 in Japanese

Drug Metab Pharmacokinet. 2006 Oct;21(5):395-405. doi: 10.2133/dmpk.21.395.


Chimeric REP7/6 has been used as a marker of CYP2D6 deletion, such as for CYP2D6*5. However, the CYP2D6*10D (*10D) haplotype found in a Japanese population consist of CYP2D6*10B, CYP2D7P-derived 3'-flanking region, and a chimeric repetitive sequence, CYP-REP7/6 (REP7/6) (Ishiguro et al. Clin. Chim. Acta. 2004: 347, 217-221). From our analysis, REP7/6 was found in 26 out of 254 Japanese subjects. Thus, the REP7/6-containing CYP2D6 genes (2D6-REP7/6) were analyzed in detail. In order to specifically detect the 2D6-REP7/6 structure, primers were designed in CYP2D6 intron 6 and the REP7/6 3'-flanking region. Among 26 subjects analyzed by PCR, 5 had 2D6-REP7/6. The other 21 subjects were confirmed to have *5 by another *5-specific primer set. Three out of five subjects with 2D6-REP7/6 had the *10D structure. However, further analysis by PCR and sequencing revealed that their haplotypes were further divided into tandem-type *36-*10D (n=2) and single-type *10D (n=1). The remaining two subjects had a novel type of a *36-containing defective structure that consists of CYP2D6*36 and 3'-flanking REP7/6 (single-type *36-REP7/6). Then, REP7/6 sequences in *5, *10D, *36-*10D, and single-type *36 were determined and classified into 5 types: types A to D for *5, type E for *10D and *36-*10D, and type F for *36. These findings could be useful for accurate determination of *5 and REP7/6-harboring aberrant CYP2D6 haplotypes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People / genetics
  • Base Sequence
  • Cytochrome P-450 CYP2D6 / genetics*
  • DNA / chemistry
  • DNA / genetics
  • Gene Deletion
  • Gene Frequency
  • Genetic Variation / genetics*
  • Genetics, Population
  • Genotype
  • Haplotypes / genetics*
  • Humans
  • Japan
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Polymorphism, Genetic / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Repetitive Sequences, Nucleic Acid / genetics*
  • Sequence Analysis, DNA


  • DNA
  • Cytochrome P-450 CYP2D6

Associated data

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