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

被引:174
作者
Lovlie, R
Daly, AK
Molven, A
Idle, JR
Steen, VM
机构
[1] HAUKELAND UNIV HOSP,CTR MOL MED,DR EINAR MARTENS RES GRP BIOL PSYCHIAT,N-5021 BERGEN,NORWAY
[2] UNIV NEWCASTLE,SCH MED,DEPT PHARMACOL SCI,PHARMACOGENET RES UNIT,NEWCASTLE TYNE NE2 4HH,TYNE & WEAR,ENGLAND
[3] NORWEGIAN UNIV SCI & TECHNOL,INST CANC RES & MOL BIOL,N-7005 TRONDHEIM,NORWAY
关键词
CYP2D6; genotyping; debrisoquine; 4-hydroxylase; gene duplication; long-PCR; ultrarapid metabolizer;
D O I
10.1016/0014-5793(96)00779-X
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
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.
引用
收藏
页码:30 / 34
页数:5
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