Chip-Based Genotyping: Translation of Pharmacogenetic Research to Clinical Practice

Abstract

The observation of interindividual differences in drug tolerance is perhaps as old as pharmacotherapy itself. Since the 1950s several monogenetic traits have been described that explain differences in drug response or drug toxicity in population subsets (1). These early discoveries have evolved into our current understanding of pharmacogenetics as a complex trait. Therapy selection guided by gene test, however, has still not made the transition into clinical practice. In the current issue of Clinical Chemistry , Daly et al. (2) present a dedicated single-microarray assay, or gene chip, for comprehensive genotyping of potentially thousands of variants in genes involved in drug metabolism, excretion, and transport. These expanded capabilities are necessary because of the complexity of drug disposition. Single polymorphisms alone do not adequately predict drug disposition because multiple routes of metabolism or transport may compensate for deficiencies in a single pathway (3). For example, the anticancer drug irinotecan is not only metabolized by UGT1A1 but is also a substrate for transporter molecules coded by ABCB1 , ABCC2 , ABCG2 , and SLCO1B1 (4). Comprehensive genotyping based on gene chips allows large-scale studies on the utility of validated and exploratory biomarkers. The pharmacogenetic gene chip developed by Daly et al. (2) covers the 7 valid genomic biomarkers of drug disposition listed by the US Food and Drug …