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Clinical Chemistry 44: 914-917, 1998;
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(Clinical Chemistry. 1998;44:914-917.)
© 1998 American Association for Clinical Chemistry, Inc.

Molecular Diagnostics and Genetics

Ultrarapid drug metabolism: PCR-based detection of CYP2D6 gene duplication

Linda S. W. Steijns, and Jan Van Der Weidea

Department of Clinical Chemistry, Psychiatric Hospital Veldwijk, P.O. Box 1000, 3850 BA Ermelo, The Netherlands.
a Author for correspondence. Fax (31) 341 557400; e-mail jvdweide{at}worldonline.nl.

The enzyme debrisoquine 4-hydroxylase (CYP2D6), which metabolizes many widely used drugs, is highly polymorphic. The activity of the enzyme ranges between subjects from ultrafast to a complete absence. Therefore, metabolic capacity varies, producing intersubject differences in therapeutic efficacy and side effects at standard recommended doses. Up to 7% of Caucasians may demonstrate ultrarapid drug metabolism (UM) because of inherited alleles with multiplicate functional CYP2D6 genes, causing an increased amount of enzyme to be expressed. Identification of UM subjects is of potential clinical importance for adjustment of doses in drug therapy, as well as to avoid misidentification of noncompliance. In our study, we tested recently designed PCR assays for the detection of the UM genotype. We found a 3.5% prevalence of UMs carrying duplicate active CYP2D6 genes in a population consisting of 202 psychiatric patients.




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