title: Inter-individual variation of several cytochrome P450 2D6 splice variants in human liver.
abstract: 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.
authors.affiliation: Hartwell Center for Bioinformatics and Biotechnology, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Jackie
authors.initials: J
authors.lastname: Denson
authors.forename: Yongchun
authors.initials: Y
authors.lastname: Wu
authors.forename: Wenjian
authors.initials: W
authors.lastname: Yang
authors.forename: Jiong
authors.initials: J
authors.lastname: Zhang
mesh_terms: D001483:Base Sequence; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D017931:DNA Primers; D006801:Humans; D008099:Liver / Q000201:enzymology*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012326:RNA Splicing
chemical_list: D017931:DNA Primers; D019389:Cytochrome P-450 CYP2D6