CYP2D6 is responsible for the metabolism of approximately 25% of all drugs. The expression of cytochrome P450 2D6 (CYP2D6) is influenced by a combination of factors including polymorphisms in the CYP2D6 gene. Analysis of the CYP2D6 genotype is used to personalize the medication to a patient's metabolism. Although many genotypes can be determined using standard genotype analysis, in some cases, an incomplete analysis is performed. The CYP2D6 genotype ∗1/∗4 often occurs in combination with a multiplication of the CYP2D6 gene, and is reported as (∗1/∗4)xN. Accurate determination of the multiplied gene is essential to provide a phenotype prediction for these patients. Duplication of the ∗1 gene leads to an extensive metabolizer genotype whereas multiplication of the ∗4 gene would not lead to extra functional enzyme and therefore provides an intermediate metabolizer phenotype. Here, a technique is described in which the copy numbers of both the ∗4 and ∗1 genes are determined using quantitative PCR techniques. This technique provides a method to predict the patient's CYP2D6 phenotype, and is therefore an important step toward personalized medicine.

copy number variations (CNV), CYP2D6, pharmacogenetics, ultrarapid metabolizer,
Drug Metabolism and Personalized Therapy
Erasmus MC: University Medical Center Rotterdam

Pondman, K.M, van Schaik, R.H.N, & van der Weide, J. (2018). Accurate determination of the CYP2D6 (∗1/∗4)xN genotype by quantitative PCR. Drug Metabolism and Personalized Therapy, 33(1). doi:10.1515/dmpt-2017-0007