Abstract
BackgroundAntiepileptic drugs (AEDs) are effective medications available for epilepsy. However, many patients do not respond to this treatment and become resistant. Genetic polymorphisms may be involved in the variation of AEDs response. Therefore, we conducted an updated systematic review and a meta-analysis to investigate the contribution of the genetic profile on epilepsy drug resistance.MethodsWe proceeded to the selection of eligible studies related to the associations of polymorphisms with resistance to AEDs therapy in epilepsy, published from January 1980 until November 2016, using Pubmed and Cochrane Library databases. The association analysis was based on pooled odds ratios (ORs) and 95% confidence intervals (CIs).ResultsFrom 640 articles, we retained 13 articles to evaluate the relationship between ATP-binding cassette sub-family C member 1 (ABCB1) C3435T polymorphism and AEDs responsiveness in a total of 454 epileptic AEDs-resistant cases and 282 AEDs-responsive cases. We found a significant association with an OR of 1.877, 95% CI 1.213–2.905. Subanalysis by genotype model showed a more significant association between the recessive model of ABCB1 C3435T polymorphism (TT vs. CC) and the risk of AEDs resistance with an OR of 2.375, 95% CI 1.775–3.178 than in the dominant one (CC vs. TT) with an OR of 1.686, 95% CI 0.877–3.242.ConclusionOur results indicate that ABCB1 C3435T polymorphism, especially TT genotype, plays an important role in refractory epilepsy. As genetic screening of this genotype may be useful to predict AEDs response before starting the treatment, further investigations should validate the association.
Highlights
Antiepileptic drugs (AEDs) are effective medications available for epilepsy
We excluded a total of 591 publications from the further analysis: abstract, articles showing absence of associations between polymorphisms and AEDs resistant epilepsy for insufficient data, case reports, duplicated articles, letter to the editors, meta-analysis, not epileptic studies, not human reports, researches about other treatments than AEDs, review articles and studies not related to associations between polymorphisms and AEDs resistant epilepsy (Fig. 1)
We identified the majority of polymorphisms in AEDs transporter genes: ATP-binding cassette sub-family C member 1 (ABCB1) and atp-binding cassette sub-family c member 2 (ABCC2)
Summary
Antiepileptic drugs (AEDs) are effective medications available for epilepsy. Many patients do not respond to this treatment and become resistant. Genetic polymorphisms may be involved in the variation of AEDs response. We conducted an updated systematic review and a meta-analysis to investigate the contribution of the genetic profile on epilepsy drug resistance. Most cases of epileptic patients respond to antiepileptic drugs (AEDs). About one-third of epileptic patients develop recurrent seizures, despite the efficacy of treatment at the optimal dose regimen. They are The exact mechanism of refractory epilepsy is not well understood. Two main hypotheses are potentially involved in the biological mechanism of AEDs resistance: transporter and target hypotheses. The target hypothesis contends that the changes in drug intracellular target sites
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