Laboratory of Genomics and Human Genetics, Institut Pasteur du Maroc, 20360, Casablanca, Morocco; Laboratory of Physiopathology, Molecular Genetics & Biotechnology, Faculty of Sciences Ain Chock, Health and Biotechnology Research Centre, Hassan II University of Casablanca, Maarif B.P 5366, Casablanca, Morocco.
Laboratory of Genomics and Human Genetics, Institut Pasteur du Maroc, 20360, Casablanca, Morocco; Laboratory of Biotechnology environment and health, Faculty of Science El Jadida, Morocco.
Epilepsy Res. 2022 Sep;185:106977. doi: 10.1016/j.eplepsyres.2022.106977. Epub 2022 Jul 8.
Epilepsy is a common serious brain condition characterized by the abnormal electrical activity of neurons. In most cases, epileptic patients respond to antiepileptic drugs. Approximately, one-third of patients prove medically intractable. The ABCB1 gene is a superfamily of ATP-binding cassette (ABC) transporters that encode a drug-transport protein, lead to cells and organs protects and eliminates toxic agents. We performed this meta-analysis to assess the association between G2677T/A in the ABCB1 gene and the risk of drug resistance in epileptic patients.
Two online libraries (PubMed and Scopus) were used to identify studies that report the relationship between G2677T/A polymorphism in the MDR1 gene and the risk of antiepileptic drug resistance. The meta-analysis was performed using Review Manager 5.3 software. The pooled odds ratios and 95 % confidence intervals (CIs) were calculated using a random or fixed effects model according to the heterogeneity between studies.
A total of 33 eligible studies were included in this meta-analysis which 4192 patients were drug-resistant and 5079 patients were drug-responsive. As a result, a significant association was observed in overall population for the genetic model GG+GA vs AA (OR with 95 % CI = 0,56 [0.34,0.93]; P = 0.02). The subgroup ethnicity analysis showed a significant decrease in the risk of AEDs resistance in the Caucasian population.
In conclusion, our analysis demonstrates that G2677T/A polymorphism in the ABCB1 gene decreases the risk of drug resistance. More studies are needed in the different ethnic groups to clarify the role of polymorphism in AEDs resistance.
癫痫是一种常见的严重脑部疾病，其特征是神经元异常电活动。在大多数情况下，癫痫患者对抗癫痫药物有反应。大约三分之一的患者被证明是医学上难治的。ABCB1 基因是 ABC 转运蛋白超家族的一员，其编码一种药物转运蛋白，导致细胞和器官保护和消除有毒物质。我们进行了这项荟萃分析，以评估 ABCB1 基因中的 G2677T/A 与癫痫患者药物耐药风险之间的关系。
使用两个在线文库（PubMed 和 Scopus）来确定报告 MDR1 基因中的 G2677T/A 多态性与抗癫痫药物耐药风险之间关系的研究。使用 Review Manager 5.3 软件进行荟萃分析。根据研究之间的异质性，使用随机或固定效应模型计算合并优势比和 95%置信区间（CI）。
共有 33 项符合条件的研究纳入了这项荟萃分析，其中 4192 名患者为耐药，5079 名患者为敏感。结果表明，总体人群中 GG+GA 与 AA 的遗传模型存在显著相关性（OR 及其 95%CI=0.56[0.34,0.93]；P=0.02）。亚组种族分析显示，白种人群中 AED 耐药风险显著降低。
总之，我们的分析表明 ABCB1 基因中的 G2677T/A 多态性降低了药物耐药的风险。需要在不同的种族群体中进行更多的研究，以阐明多态性在 AED 耐药中的作用。
