Clinical factors and ABCB1 polymorphisms in prediction of antiepileptic drug response: a prospective cohort study.
Lancet Neurol
; 5(8): 668-76, 2006 Aug.
Article
en En
| MEDLINE
| ID: mdl-16857572
ABSTRACT
BACKGROUND:
The ABCB1 3435C-->T single-nucleotide polymorphism (SNP) or a three-SNP haplotype containing 3435C-->T has been implicated in multidrug resistance in epilepsy in three retrospective case-control studies, but a further three have failed to replicate the association. We aimed to determine the effect of the ABCB1 gene on epilepsy drug response, using a unique large cohort of epilepsy patients with prospectively measured seizure and drug response outcomes.METHODS:
The ABCB1 3435C-->T polymorphism and three-SNP haplotype, plus a comprehensive set of tag SNPs across ABCB1 and adjacent ABCB4, were genotyped in a cohort of 503 epilepsy patients with prospectively measured seizure and drug response outcomes. Clinical, demographic, and genetic data were analysed. Treatment outcome was measured in terms of time to 12-month remission, time to first seizure, and time to drug withdrawal due to inadequate seizure control or side-effects. Randomly selected genome-wide HapMap SNPs (n=129) were genotyped in all patients for genomic control.FINDINGS:
Number of seizures before treatment was the dominant feature predicting seizure outcome after starting antiepileptic drug therapy, measured by both time to first seizure (hazard ratio 1.34, 95% CI 1.21-1.49, p<0.0001) and time to 12-month remission (0.83, 0.73-0.94, p=0.003). There was no association of the ABCB1 3435C-->T polymorphism, the three-SNP haplotype, or any gene-wide tag SNP with time to first seizure after starting drug therapy, time to 12-month remission, or time to drug withdrawal due to unacceptable side-effects or to lack of seizure control.INTERPRETATION:
We found no evidence that ABCB1 common variation influences either seizure or drug withdrawal outcomes after initiation of antiepileptic drug therapy.
Buscar en Google
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Transportadoras de Casetes de Unión a ATP
/
Polimorfismo de Nucleótido Simple
/
Epilepsia
/
Anticonvulsivantes
Tipo de estudio:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Lancet Neurol
Asunto de la revista:
NEUROLOGIA
Año:
2006
Tipo del documento:
Article
País de afiliación:
Reino Unido