KCNH2 polymorphism and methadone dosage interact to enhance QT duration.
Drug Alcohol Depend
; 141: 34-8, 2014 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-24875677
ABSTRACT
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±34ms. 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 15.4ms 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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
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8_ODS3_consumo_sustancias_psicoactivas
Base de dados:
MEDLINE
Assunto principal:
Polimorfismo de Nucleotídeo Único
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Canais de Potássio Éter-A-Go-Go
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Sistema de Condução Cardíaco
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Dependência de Heroína
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Metadona
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Entorpecentes
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Drug Alcohol Depend
Ano de publicação:
2014
Tipo de documento:
Article