Pharmacogenetic profiling of drug metabolizing enzyme genes

Abstract

Background Pharmacogenetic testing has become increasingly important in drug development and pharmaco‐vigilance processes. To understand the inter‐individual differences in active pathways, tests that target multiple drug metabolizing and drug interacting proteins are required. Method A DNA microarray was developed that consists of an array‐of arrays for genotyping 16 samples simultaneously (the DrugMEt™ Test). Genotyping is accomplished in a single reaction with allele‐specific primers for 27 SNPs of eight highly polymorphic genes: CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A5, TPMT, NAT2, and MDR1. The accuracy and reproducibility were evaluated, and a method comparison with the TaqMan™ assay was performed. The applicability of the method was investigated with samples from different ethnic backgrounds. Results For the various SNPs, an accuracy >99%, and reproducibility of >95%, was observed. The method comparison indicated >95% concordance between the DrugMEt™ Test and TaqMan™ assay. The genotype frequencies of the Caucasian, African American, and Asian populations matched those published in the literature. Conclusions The multigene DrugMEt™ microarray provides a straight‐forward basis for the selection of a drug compound for future development, and identification of the potential responder population. Moreover, drug‐interacting pathways may be identified. Clinical Pharmacology & Therapeutics (2005) 77, P64–P64; doi:

Impact of genotype on adverse effects during treatment with metoprolol: A prospective clinical study

“…Genotyping for the alleles *3 , *4 , *6 to *8 , and *10 was performed by use of predeveloped TaqMan Assay‐Reagents Allelic Discrimination Kits (Applied Biosystems, Foster City, Calif). TaqMan assays established and validated in our laboratory were used for genotyping of *9 and *41 17 , 28 . The CYP2D6*5 allele and gene duplications were determined as previously described 29 .…”

“…Taq-Man assays established and validated in our laboratory were used for genotyping of *9 and *41. 17,28 The CYP2D6*5 allele and gene duplications were determined as previously described. 29 Individuals were classified as PMs if they carried any 2 of the nonfunctional alleles.…”