CYP2D7 splice variants in human liver and brain: does CYP2D7 encode functional protein?

Biochem Biophys Res Commun. 2005 Nov 4;336(4):1241-50. doi: 10.1016/j.bbrc.2005.08.255.

Abstract

A CYP2D7 brain-specific protein metabolizing codeine and encoded by an alternate mRNA has recently been described in Indian subjects. To examine its potential presence in other ethnic backgrounds, CYP2D7 and CYP2D6 full-length splice products were analyzed in liver and brain. CYP2D7 splice variant-specific PCR on 13 subjects revealed the previously reported partial intron 6-containing transcript encoding CYP2D7 in both tissues as a minor variant. This transcript is not predicted to encode functional protein as a frame-shift-reverting deletion in CYP2D7 exon 1 (138delT) was not detected in any transcript or in 285 additional genotyped subjects. The g.14408G > C SNP required for functional transcript also was not observed; all transcripts and individuals genotyped as g.14408G/G that causes a premature stop codon in any splice variants that contain the 57bp intron 6 insertion. Therefore, no evidence for functional CYP2D7 transcripts was observed in Asian, Caucasian or African American individuals.

MeSH terms

  • African Continental Ancestry Group
  • Alternative Splicing*
  • Asian Continental Ancestry Group
  • Brain / metabolism
  • Cytochrome P-450 CYP2D6 / genetics*
  • Cytochrome P-450 CYP2D6 / metabolism
  • Cytochrome P-450 Enzyme System / genetics*
  • Cytochrome P-450 Enzyme System / metabolism
  • European Continental Ancestry Group
  • Exons
  • Genotype
  • Humans
  • Introns
  • Liver / metabolism
  • Polymorphism, Single Nucleotide*
  • RNA, Messenger / genetics

Substances

  • RNA, Messenger
  • cytochrome P-450 CYP2D7P
  • Cytochrome P-450 Enzyme System
  • Cytochrome P-450 CYP2D6