Ultrarapid metabolizers of debrisoquine: characterization and PCR-based detection of alleles with duplication of the CYP2D6 gene.
Up to 7% of Caucasians may demonstrate ultrarapid metabolism of debrisoquine due to inheritance of alleles with duplicated functional CYP2D6 genes. Here we describe the genomic organization of the duplicated CYP2D6 genes in the 42 kb XbaI allele. We postulate that this duplication originates from a homologous, unequal cross-over event which involved two 29 kb XbaI wild-type alleles, and had break points within a 2.8 kb direct repeat (CYP-REP) flanking the CYP2D6 gene. Moreover, we have designed two different PCR assays for detection of alleles with duplicated CYP2D6 genes. Both assays correctly identified 29 out of 29 subjects positive for the 42 kb XbaI allele. No false negative or false positive reactions were observed.
Løvlie
R
R
Center for Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
Daly
A K
AK
Molven
A
A
Idle
J R
JR
Steen
V M
VM
D000483:Alleles; D001483:Base Sequence; D003434:Crossing Over, Genetic; D019389:Cytochrome P-450 CYP2D6; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004247:DNA; D003647:Debrisoquin / Q000378:metabolism*; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family; D016133:Polymerase Chain Reaction / Q000379:methods*
D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019389:Cytochrome P-450 CYP2D6; D003647:Debrisoquin