Pharmacogenetics of drug-induced arrhythmias: a feasibility study using spontaneous adverse drug reactions reporting data
| Autor: | Hubert G. M. Leufkens, Madelon Bracke, Eugène van Puijenbroek, Marie L. De Bruin, Arno W. Hoes |
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| Rok vydání: | 2006 |
| Předmět: |
Adult
Male Drug ERG1 Potassium Channel medicine.medical_specialty Drug-Related Side Effects and Adverse Reactions Epidemiology media_common.quotation_subject Buccal swab Muscle Proteins Pharmacogenetic Study Sodium Channels NAV1.5 Voltage-Gated Sodium Channel Internal medicine Pharmacovigilance medicine Adverse Drug Reaction Reporting Systems Humans Genetic Predisposition to Disease Pharmacology (medical) Netherlands media_common business.industry Public health Case-control study Arrhythmias Cardiac Middle Aged Ether-A-Go-Go Potassium Channels Long QT Syndrome Pharmacogenetics Potassium Channels Voltage-Gated Case-Control Studies Anesthesia Mutation Feasibility Studies Female business |
| Zdroj: | Pharmacoepidemiology and Drug Safety. 15:99-105 |
| ISSN: | 1099-1557 1053-8569 |
| DOI: | 10.1002/pds.1194 |
| Popis: | SUMMARY Purpose The bottleneck in pharmacogenetic research on rare adverse drug reactions (ADR) is retrieval of patients. Spontaneous reports of ADRs may form a useful source of patients. We investigated the feasibility of a pharmacogenetic study, in which cases were selected from the database of a spontaneous reporting system for ADRs, using drug-induced arrhythmias as an example. Methods Reports of drug-induced arrhythmias to proarrhythmic drugs were selected from the database of the Netherlands Pharmacovigilance Centre (1996–2003). Information on the patient’s general practitioner (GP) was obtained from the original report, or from another health care provider who reported the event. GPs were contacted and asked to recruit the patient as well as two age, gender and drug matched controls. Patients were asked to fill a questionnaire and provide a buccal swab DNA sample through the mail. DNA samples were screened for 10 missense mutations in 5 genes associated with the congenital long-QT (LQT) syndrome (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2). Results We identified 45 eligible cases, 29 GPs could be contacted of which seven were willing to participate. Four cases and five matched controls could be included in the study, giving an overall participation rate of 9% (4/45). The main reason for GPs not being willing to participate was lack of time. Variants were identified in KCNH2, SCN5A and KCNE1. Conclusions Spontaneous reporting systems for ADRs may be used for pharmacogenetic research. The methods described, however, need to be improved to increase participation and international collaboration may be required. Copyright # 2005 John Wiley & Sons, Ltd. |
| Databáze: | OpenAIRE |
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