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Toxicologic Pathology, Vol. 32, No. 1 suppl, 9-12 (2004)
DOI: 10.1080/01926230490424743

Pharmacogenetics to Predict Drug-Related Adverse Events

David A. Hosford

Department of Genetics Research, david.hosford{at}gsk.com

Eric H. Lai

Department of Genetics Research

John H. Riley

Department of Genetics Research

Chun-Fang Xu

Department of Genetics Research

Theodore M. Danoff

Department of Clinical Pharmacology and Discovery Medicine

Allen D. Roses

Department of Genetics Research

Identification of reliable markers to predict drug-related adverse events (DRAEs) is an important goal of the pharmaceutical industry and others within the healthcare community. We have used genetic polymorphisms, including the most frequent source of variation (single nucleotide polymorphisms, SNPs) in the human genome, in pharmacogenetic approaches designed to predict DRAEs. Three studies exemplify the principles of using polymorphisms to identify associations in progressively larger genomic regions: polymorphic repeats within the UDP-glucuronysltransferase I (UGT1A1) gene in patients experiencing hyperbilirubinemia after administration of tranilast, an experimental drug to prevent re-stenosis following coronary revascularization; high linkage disequilibrium within the Apolipoprotein E (ApoE) gene in patients with Alzheimer Disease (AD); and the polymorphic variant HLA-B57 in patients with hypersensitivity reaction after administration of abacavir, a nucleoside reverse transcriptase inhibitor for the treatment of HIV. Together, these studies demonstrate in a stepwise manner the feasibility of using pharmacogenetic approaches to predict DRAEs.

Key Words: Pharmacogenetics • adverse drug reaction • drug-related adverse event • single nucleotide polymorphism • Gilbert's syndrome • Tranilast • Apolipoprotein E • Alzheimer's Disease • abacavir • hypersensitivity reaction.


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