Ultrarapid metabolizers of debrisoquine: Characterization and PCR‐based detection of alleles with duplication of the CYP2D6 gene

FEBS Letters

Daly, Ann K.¹  Idle, Jeffrey R.¹  Løvlie, Roger²  Molven, Anders²  Steen, Vidar M.² 

[1] Pharmacogenetics Research Unit, Department of Pharmacological Sciences, University of Newcastle, Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK;Dr. Einar Martens' Research Group for Biological Psychiatry, Center for Molecular Medicine, Haukeland University Hospital, N-5021 Bergen, Norway

关键词: CYP2D6 genotyping;    Debrisoquine 4-hydroxylase;    Gene duplication;    Long-PCR;    Ultrarapid metabolizer;    CYP;    cytochrome P450;    MR;    metabolic ratio;    PM;    poor metabolizer;    RFLP;    restriction fragment length polymorphism;    UM;    ultrarapid metabolizer;   

DOI  :  10.1016/0014-5793(96)00779-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown