Genome-wide approaches to identify pharmacogenetic contributions to adverse drug reactions
| Autor: | Michael Mosteller, Li Li, Eric H. Lai, Silviu-Alin Bacanu, Allen D. Roses, Clive E. Bowman, Matthew R. Nelson, Margaret G. Ehm |
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| Rok vydání: | 2008 |
| Předmět: |
Drug-Related Side Effects and Adverse Reactions
Population Pharmacology Bioinformatics Polymorphism Single Nucleotide Genome Drug Hypersensitivity Health care Genetics Humans Medicine Drug reaction education Genotyping Clinical Trials as Topic education.field_of_study Genome Human business.industry DNA Dideoxynucleosides Clinical trial HLA-B Antigens Pharmacogenetics Molecular Medicine Single nucleotide polymorphism analysis business |
| Zdroj: | The Pharmacogenomics Journal. 9:23-33 |
| ISSN: | 1473-1150 1470-269X |
| Popis: | Adverse drug reactions (ADRs) have a major impact on patients, physicians, health care providers, regulatory agencies and pharmaceutical companies. Identifying the genetic contributions to ADR risk may lead to a better understanding of the underlying mechanisms, identification of patients at risk and a decrease in the number of events. Technological advances have made the routine monitoring and investigation of the genetic basis of ADRs during clinical trials possible. We demonstrate through simulation that genome-wide genotyping, coupled with the use of clinically matched or population controls, can yield sufficient statistical power to permit the identification of strong genetic predictors of ADR risk in a prospective manner with modest numbers of ADR cases. The results of a 500,000 single nucleotide polymorphism analysis of abacavir-associated hypersensitivity reaction suggest that the known HLA-B gene region could be identified with as few as 15 cases and 200 population controls in a sequential analysis. |
| Databáze: | OpenAIRE |
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