Association of an ABCB1 gene haplotype with pharmacoresistance in temporal lobe epilepsy

Zimprich, Fritz; Sunder‐Plaßmann, Raute; Stögmann, Elisabeth; Gleiß, Andreas; Dal‐Bianco, Assunta; Zimprich, Alexander; Plumer, S.; Baumgartner, Christian; Mannhalter, Christine

doi:10.1212/01.wnl.0000141021.42763.f6

Cited by 158 publications

(125 citation statements)

References 11 publications

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“…Another study 83 partially replicated the initial finding, this time in a cohort of 193 ethnically similar patients with temporal lobe epilepsy. Patients were stratified into three outcome groups:…”

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confidence: 62%

“…These inconsistent results may be due to several factors. First, both replicating ABCB1 genotype and therapeutic drug response GD Leschziner et al studies were based either solely on temporal lobe epilepsy, 83 or were mainly temporal lobe epilepsy patients, 86 and it is conceivable that the association is only true in this subgroup of patients. Secondly, the definition of outcome has varied between studies, the exception being the Tan et al study, 82 which still failed to replicate the original finding.…”

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confidence: 99%

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ABCB1 genotype and PGP expression, function and therapeutic drug response: a critical review and recommendations for future research

et al. 2006

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The product of the ABCB1 gene, P-glycoprotein (PGP), is a transmembrane active efflux pump for a variety of drugs. It is a putative mechanism of multidrug resistance in a range of diseases. It is postulated that ABCB1 polymorphisms contribute to variability in PGP function, and that therefore multidrug resistance is, at least in part, genetically determined. However, studies of ABCB1 genotype or haplotype and PGP expression, activity or drug response have produced inconsistent results. This critical review of ABCB1 genotype and PGP function, including mRNA expression, PGP-substrate drug pharmacokinetics and drug response, highlights methodological limitations of existing studies, including inadequate power, potential confounding by co-morbidity and co-medication, multiple testing, poor definition of disease phenotype and outcomes, and analysis of multiple drugs that might not be PGP substrates. We have produced recommendations for future research that will aid clarification of the association between ABCB1 genotypes and factors related to PGP activity.

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confidence: 62%

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confidence: 99%

ABCB1 genotype and PGP expression, function and therapeutic drug response: a critical review and recommendations for future research

et al. 2006

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“…The 3435C4T polymorphism in the ABCB1 drug transporter gene, or a haplotype that includes this variation, has been correlated with lack of efficacy to multiple AEDs. [9][10][11] Although these findings have not been confirmed by all investigators, 12,13 such work has the potential to identify patients who could be early candidates for non-AED treatments such as brain stimulation or surgery. With improved understanding of AED transport mechanisms, it may also be possible to develop methods of circumventing drug efflux transporters, and improve access of AEDs to critical sites of action in the brain.…”

Section: Predicting Refractory Epilepsymentioning

confidence: 99%

Defining the clinical role of pharmacogenetics in antiepileptic drug therapy

2006

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“…Siddiqui et al [24] were the first to show that the CC genotype of ABCB1 3435C>T was associated with poor response to AED. However, subsequent studies were controversial regarding the association between the genetic variations of ABCB1 in individuals and the response to AEDs [25][26][27][28][29][30][31]. Furthermore, both a prospective study and a study using whole genome approach failed to replicate the original report [32,33].…”

Section: Genetic Variations In Individuals That May Affect Pharmacokimentioning

confidence: 99%

Genetic variations and response to antiepileptic drug

Kim

2010

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Despite the state-of-the-art medical treatment with antiepileptic drugs (AED), at least one-third of newly diagnosed epilepsy patients may show poor response to AED. Although the biological mechanism of diverse responses to AED is poorly understood, it is likely that multifactorial factors could be responsible for the different responses. Clinical factors such as etiology of epilepsy and pre-treatment seizure frequency can predict the different responses to AED, whereas the role of genetic variations in individuals contributing to variation in response to AED is still conflicting. The inconsistency in proving the genetic roles in different responses to AED may be partly explained by (1) diversity of the definition of response to AED, (2) heterogeneity of the subjects, and (3) lack of multigenetic approach. While we hypothesize that the genetic variations in individuals may independently contribute to different responses to AED, multigenetic interactions including both the genetic variations of pharmacokinetics and pharmacodynamics may take place.

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Association of an ABCB1 gene haplotype with pharmacoresistance in temporal lobe epilepsy

Cited by 158 publications

References 11 publications

ABCB1 genotype and PGP expression, function and therapeutic drug response: a critical review and recommendations for future research

ABCB1 genotype and PGP expression, function and therapeutic drug response: a critical review and recommendations for future research

Defining the clinical role of pharmacogenetics in antiepileptic drug therapy

Genetic variations and response to antiepileptic drug

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