Accurate determination of the CYP2D6 (∗1/∗4)xN genotype by quantitative PCR

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.