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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
KCNH2 polymorphism and methadone dosage interact to enhance QT duration
Drug and Alcohol Dependence, Volume 141, Year 2014
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Description
Background: Many drugs increase the duration of the QT interval of patients, potentially leading to harmful effects such as polymorphic ventricular arrhythmias. Most of these drugs do so by inhibiting the rapid component IKr of the delayed rectifier potassium current IK. Methadone is the most prescribed heroin maintenance treatment and is known to inhibit the cardiac potassium channel hERG, which recapitulates IKr. In order to evaluate if any polymorphism of potassium channels' genes could explain some of the "idiosyncratic" QT prolongations observed in patients treated with methadone, we tested the association between KCNE1, KCNE2, and KCNH2 polymorphism and the QT interval prolongation in those patients, controlling for other variables associated with a decrease of the repolarizing reserve. Methods: A cohort of 82 patients treated with stable dosage of methadone (mean dosage 65. mg/d) for at least three months was genotyped for five polymorphisms in KCNE1, KCNE2 and KCNH2 genes and had their corrected QT (QTc) assessed. Results: The mean QTc interval was 415. ±. 34. ms. In a linear regression model, longer QTc interval was associated with methadone dosage and with one genetic factor. Each copy of a Lys allele at codon 897 of KCNH2, the gene that encodes the cardiac potassium voltage-gated channel hERG, was associated with a 15.4. ms longer QTc (95% CI [4.6-26.2]; p= 0.001). Conclusion: KCNH2 genotyping may be relevant in the analysis of cumulative risk factors for QT prolongation in patients on methadone maintenance treatment. © 2014 Elsevier Ireland Ltd.
Authors & Co-Authors
Hajj, Aline
France, Paris
Optimisation Thérapeutique en Neuropsychopharmacologie
France, Paris
Service de Biochimie
Lebanon, Beirut
Université Saint-joseph de Beyrouth
Ksouda, Kamilia
France, Paris
Optimisation Thérapeutique en Neuropsychopharmacologie
France, Paris
Service de Psychiatrie
Peoc'h, Katell
France, Paris
Optimisation Thérapeutique en Neuropsychopharmacologie
France, Paris
Service de Biochimie
Curis, Emmanuel
France, Paris
Optimisation Thérapeutique en Neuropsychopharmacologie
France, Paris
Université Paris Cité
Messali, Anne
France, Paris
Serv. Cardiol.
Deveaux, Laurence Labat
France, Paris
Hôpital Hotel-dieu Ap-hp
Bloch, Vanessa
France, Paris
Optimisation Thérapeutique en Neuropsychopharmacologie
Prince, Nathalie
France, Paris
Optimisation Thérapeutique en Neuropsychopharmacologie
Mouly, St́ephane J.
France, Paris
Optimisation Thérapeutique en Neuropsychopharmacologie
Scherrmann, Jean Michel
France, Paris
Optimisation Thérapeutique en Neuropsychopharmacologie
Lépine, Jean Pierre
France, Paris
Optimisation Thérapeutique en Neuropsychopharmacologie
France, Paris
Service de Psychiatrie
Laplanche, Jean Louis
France, Paris
Optimisation Thérapeutique en Neuropsychopharmacologie
France, Paris
Service de Biochimie
Drici, Milou Daniel
France, Nice
Laboratoire de Pharmacologie
Vorspan, Florence
France, Paris
Optimisation Thérapeutique en Neuropsychopharmacologie
France, Paris
Service de Psychiatrie
Statistics
Citations: 17
Authors: 14
Affiliations: 8
Identifiers
Doi:
10.1016/j.drugalcdep.2014.04.027
ISSN:
03768716
e-ISSN:
18790046
Research Areas
Genetics And Genomics
Noncommunicable Diseases
Study Design
Cohort Study