Comprehensive assessment of metabolic enzyme and transporter genes using the Affymetrix^® Targeted Genotyping System

Authors: Dumaual, Carmen; Miao, Xin; Daly, Thomas M; Bruckner, Carsten; Njau, Reuben; Fu, Dong-Jing; Close-Kirkwood, Sandra; Bauer, Nancy; Watanabe, Nancy; Hardenbol, Paul; Hockett, Richard D

Source: Pharmacogenomics, Volume 8, Number 3, March 2007 , pp. 293-305(13)

Publisher: Future Medicine

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Abstract:

The combined effects of multiple polymorphisms in several drug-metabolizing enzyme and transporter genes can contribute to considerable interindividual variation in drug disposition and response. Therefore, it has been of increasing interest to generate scalable, flexible and cost-effective technologies for large-scale genotyping of the drug-metabolizing enzyme and transporter genes. However, the number of drug-metabolizing enzyme and transporter gene variants exceeds the capacity of current technologies to comprehensively assess multiple polymorphisms in a single, multiplexed assay. The Targeted Genotyping System (Affymetrix^®, CA, USA) provides a solution to this challenge, by combining molecular inversion probe technology with universal microarrays to provide a method that is capable of analyzing thousands of variants in a single reaction, while remaining relatively insensitive to cross-reactivity between reaction components. This review will focus on the Targeted Genotyping System and how this technology was adapted to enable comprehensive analysis of drug-metabolizing enzyme and transporter gene polymorphisms.

Keywords: cytochrome P450; drug metabolism; genotyping; molecular inversion probe; multiplex; polymorphism; SNP

Document Type: Research article

DOI: http://dx.doi.org/10.2217/14622416.8.3.293

Affiliations: 1: 1Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA., Email: hockettrd@lilly.com

Publication date: 2007-03-01

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