Chouchi Malek, Kaabachi Wajih, Klaa Hedia, Tizaoui Kalthoum, Turki Ilhem Ben-Youssef, Hila Lamia
Department of Genetic, Tunis El Manar University, Faculty of Medicine of Tunis, 15 Jebel Lakhdhar street, La Rabta, 1007, Tunis, Tunisia.
Department of Child Neurology, National Institute Mongi Ben Hmida of Neurology, UR12SP24 Abnormal Movements of Neurologic Diseases, Jebel Lakhdhar street, La Rabta, 1007, Tunis, Tunisia.
BMC Neurol. 2017 Feb 15;17(1):32. doi: 10.1186/s12883-017-0801-x.
Antiepileptic 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.
We 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).
From 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.
Our 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.
抗癫痫药物（AEDs）是可用于治疗癫痫的有效药物。然而，许多患者对这种治疗无反应并产生耐药性。基因多态性可能与AEDs反应的差异有关。因此，我们进行了一项更新的系统评价和荟萃分析，以研究基因谱对癫痫耐药性的影响。
我们使用PubMed和Cochrane图书馆数据库，筛选了1980年1月至2016年11月发表的与癫痫中基因多态性与AEDs治疗耐药性关联相关的合格研究。关联分析基于合并比值比（ORs）和95%置信区间（CIs）。
从640篇文章中，我们保留了13篇文章，以评估ATP结合盒亚家族C成员1（ABCB1）C3435T多态性与AEDs反应性之间的关系，共纳入454例癫痫AEDs耐药病例和282例AEDs反应性病例。我们发现存在显著关联，OR为1.877，95%CI为1.213 - 2.905。按基因型模型进行的亚组分析显示，ABCB1 C3435T多态性的隐性模型（TT与CC）与AEDs耐药风险之间的关联更为显著，OR为2.375，95%CI为1.775 - 3.178，而显性模型（CC与TT）的OR为1.686，95%CI为0.877 - 3.242。
我们的结果表明，ABCB1 C3435T多态性，尤其是TT基因型，在难治性癫痫中起重要作用。由于对该基因型的基因筛查可能有助于在开始治疗前预测AEDs反应，因此需要进一步研究来验证这种关联。
