5th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 8–11 July 2003, Le Meridien Montparnasse, Paris, France

PHARMACOGENOMICS: THE INHERITED BASIS FOR INTER-INDIVIDUAL DIFFERENCES IN DRUG RESPONSE

Antiviral Therapy 2003; 8:L3 (abstract P6)

WE Evans
St. Jude Children’s Research Hospital, Memphis, TN, USA

Most medications exhibit wide inter-patient variability in their efficacy and toxicity. For many medications, these inter-individual differences are due in part to polymorphisms in genes encoding drug metabolizing enzymes, drug transporters and/or drug targets (e.g., receptors, enzymes). Pharmacogenomics is a burgeoning field aimed at elucidating the genetic basis for differences in drug efficacy and toxicity, using genomewide approaches to identify the network of genes that govern an individual’s response to drug therapy. For some genetic polymorphisms (e.g., thiopurine S-methyltransferase, TPMT), monogenic traits have a marked effect on pharmacokinetics (e.g., drug metabolism), such that individuals who inherit an enzyme deficiency must be treated with markedly different doses of the affected medications (e.g., 5–10% of the standard thiopurine dose). Likewise, polymorphisms in drug targets (e.g., β adrenergic receptors) can alter the sensitivity of patients to treatment (e.g., β-agonists), changing the pharmacodynamics of drug response. Recognizing that most pharmacological effects are determined by the interplay of several gene products that govern the pharmacokinetics and pharmacodynamics of medications, pharmacogenomics research aims to elucidate these polygenic determinants of drug effects, and to development of new medications. The ultimate goal is to provide new strategies for discovery and optimization of drug therapy based on each patient’s genetic determinants of drug efficacy and toxicity. This presentation will use the TPMT polymorphism and thiopurine (e.g., azathioprine) therapy to illustrate the potential of pharmacogenomics to elucidate genetic determinants of drug response, and optimize the selection of drug therapy for individual patients (reviewed in Evans & Relling, Science. 1999 Oct 15;286(5439):487-91; Evans & McLeod, N Engl J Med. 2003 Feb 6;348(6):553-6.

Presenting author: WE Evans

2003-07-08
P6

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