title: CYP2D7 splice variants in human liver and brain: does CYP2D7 encode functional protein?
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.
authors.affiliation: Division of Clinical Pharmacology and Experimental Therapeutics, The Children's Mercy Hospital and Clinics, Kansas City, MO, USA. agaedigk@cmh.edu
authors.forename: Andrea
authors.initials: A
authors.lastname: Gaedigk
authors.forename: Roger
authors.initials: R
authors.lastname: Gaedigk
authors.forename: J Steven
authors.initials: JS
authors.lastname: Leeder
mesh_terms: D017398:Alternative Splicing; D044466:Asian People; D044383:Black People; D001921:Brain / Q000378:metabolism; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D005838:Genotype; D006801:Humans; D007438:Introns; D008099:Liver / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics; D044465:White People; D001741:Black or African American
chemical_list: D012333:RNA, Messenger; C102835:cytochrome P-450 CYP2D7P; D003577:Cytochrome P-450 Enzyme System; D019389:Cytochrome P-450 CYP2D6