Sporis Davor, Bozina Nada, Basić Silvio, Lovrić Mila, Babić Tomislav, Susak Ivana, Marković Ivana
University of Zagreb, Dubrava University Hospital, Department of Neurology, Zagreb, Croatia.
Coll Antropol. 2013 Mar;37(1):41-5.
Despite advances in antiepileptic drug (AED) therapy, about one-third of patients with epilepsy are resistant to drug treatment. Functional impact of polymorphisms in drug-efflux transporter genes may contribute to multidrug resistance theory. Studies on ABCB1 gene gave contradictory results and available data suggest that this polymorphism may not directly cause altered P-glycoprotein (Pgp) transport activity but may be associated with one or more causal variants in the stretch of linkage disequilibrium or is caused by multiple gene polymorphisms. Genetic polymorphisms also occur frequently in other transmembrane transport systems including the multidrug resistance proteins (MRPs, ABCC2). The aim of this research was to investigate the possible association of ABCC2 gene polymorphisms G1249A in exon 10 and C24T in exon 1 with the development of drug resistance. This cross-sectional study is a part of ongoing pharmacogenomic study of epilepsy in Croatian population. All patients enrolled in the study had an established diagnosis of partial complex epilepsy with or without secondary generalization with non lesional brain MRI with epilepsy protocol and have been suffering for more than two years. They were divided into two groups. The first group comprised 52 patients refractory to the current therapy, while the second group consisted of 45 patients with well-controlled seizures. Our data did not identify any significant association between genetic polymorphisms of exon 1 (24C > T) and exon 10 (1249G < A) of ABCC2 gene or any combined effect in response to AED treatment and development of drug resistance in patients with partial complex epilepsy. Statistical significant difference was not found in genotype based analysis, allele frequency, haplotype and combined genotype analysis.
尽管抗癫痫药物（AED）治疗取得了进展，但约三分之一的癫痫患者对药物治疗耐药。药物外排转运蛋白基因多态性的功能影响可能有助于多药耐药理论。关于ABCB1基因的研究结果相互矛盾，现有数据表明，这种多态性可能不会直接导致P-糖蛋白（Pgp）转运活性改变，但可能与连锁不平衡区域中的一个或多个因果变异相关，或者由多个基因多态性引起。基因多态性在包括多药耐药蛋白（MRPs，ABCC2）在内的其他跨膜转运系统中也经常出现。本研究的目的是调查ABCC2基因第10外显子的G1249A和第1外显子的C24T多态性与耐药性发展之间的可能关联。这项横断面研究是克罗地亚人群正在进行的癫痫药物基因组学研究的一部分。所有纳入研究的患者均已确诊为伴有或不伴有继发性全身性发作的部分性复杂性癫痫，脑部MRI无病变且采用癫痫方案，病程超过两年。他们被分为两组。第一组包括52例对当前治疗难治的患者，而第二组由45例癫痫发作得到良好控制的患者组成。我们的数据未发现ABCC2基因第1外显子（24C>T）和第10外显子（1249G<A）的基因多态性之间存在任何显著关联，也未发现对AED治疗的反应与部分性复杂性癫痫患者耐药性发展之间存在任何联合效应。在基于基因型的分析、等位基因频率、单倍型和联合基因型分析中未发现统计学显著差异。
