1. ¹GlaxoSmithKline, RTP, NC, USA
2. ²National Institute of Environmental Health Sciences, RTP, NC, USA
3. ³GlaxoSmithKline, Harlow, Essex, UK

Correspondence: Dr M Mosteller, Genetic Analysis, Genetic Research, GlaxoSmithKline, Five Moore Drive, RTP, NC 27709, USA. E-mail: mike.m.mosteller@gsk.com

Received 28 February 2006; Revised 13 July 2006; Accepted 24 July 2006; Published online 12 September 2006.

Abstract

The objective of pharmacogenetic research is to identify a genetic marker, or a set of genetic markers, that can predict how a given person will respond to a given medicine. To search for such marker combinations that are predictive of adverse drug events, we have developed and applied two complementary methods to a pharmacogenetic study of the hypersensitivity reaction (HSR) associated with treatment with abacavir, a medicine that is used to treat HIV-infected patients. Our results show that both of these methods can be used to uncover potentially useful predictive marker combinations. The pairwise marker combination method yielded a collection of marker pairs that featured a spectrum of sensitivities and specificities. Recursive partitioning results led to the genetic delineation of multiple risk categories, including those with extremely high and extremely low risk of HSR. These methods can be readily applied in pharmacogenetic candidate gene studies as well as in genome-wide scans.