PCR-based genotyping for duplicated and deleted CYP2D6 genes

Abstract

The debrisoquine hydroxylase (CYP2D6), which metabolizes more than 30 different drugs, is highly polymorphic. In subjects having either very low or very high enzyme activity, drug therapy at recommended doses using CYP2D6 substrates may lead to either increased risk of side effects or therapeutic failure. We here describe PCR-based methods for detection of alleles having either duplicated, multiduplicated or deleted active CYP2D6 genes. As a control reaction, the entire coding region of the CYP2D6 gene is amplified. In conjunction with analysis of common mutations using this product as a template, the methods described can be used for genotyping of individuals being either poor, intermediate rapid, normal or ultrarapid metabolizers and provides an efficient tool for individualization of drug therapy.