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

Background:CYP2D6is 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 theCYP2D6gene. Analysis of theCYP2D6genotype 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. TheCYP2D6genotype *1/*4 often occurs in combination with a multiplication of theCYP2D6gene, 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.Methods:Here, a technique is described in which the copy numbers of both the *4 and *1 genes are determined using quantitative PCR techniques.Results and conclusions:This technique provides a method to predict the patient’sCYP2D6phenotype, and is therefore an important step toward personalized medicine.