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 debris oquine due to inheritance of alleles with duplicated functional CYP2D6 genes, Here we describe the genomic organization of the duplicated CY P2D6 genes in the 42 kb XbaI allele. We postulate that this duplicatio n originates from a homologous, unequal cross-over event which involve d 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 dupli cated CYP2D6 genes, Both assays correctly identified 29 out of 29 subj ects positive for the 42 kb XbaI allele. No false negative or false po sitive reactions were observed.