Inter-individual variation of several cytochrome P450 2D6 splice variants in human liver

Biochem Biophys Res Commun. 2005 May 6;330(2):498-504. doi: 10.1016/j.bbrc.2005.03.010.


To examine the possibility that inter-individual differences in splicing partially explain the observed differences in CYP2D6 activity, we amplified its full-length cDNA in 96 human liver RNA samples and discovered five splice variants: intron 5 retention, intron 6 retention, intron 5 and intron 6 double retention, exon 3 skipping, and partial intron 1 retention. All of the CYP2D6 splice variants we identified are probably nonfunctional transcripts. Substantial inter-individual variation in the proportions of the CYP2D6 transcript represented by splice variants, measured by real-time PCR, suggests that the presence of these splice variants contributes to the population variation in CYP2D6 activity. Relatively high levels of intron 6 retention were not correlated with the newly discovered single nucleotide polymorphism 2988G > A in intron 6 (CYP2D6*41) but did correlate with the more common CYP2D6*34 allele. Our study prompts further investigations to explore the effect of these splice variants on drug metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cytochrome P-450 CYP2D6 / genetics*
  • DNA Primers
  • Humans
  • Liver / enzymology*
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide
  • RNA Splicing*


  • DNA Primers
  • Cytochrome P-450 CYP2D6