Department of Pharmacology, School of Medicine, the University of Jordan, Amman, Jordan.
Department of Biopharmaceutics and Clinical Pharmacy, School of Pharmacy, the University of Jordan, Amman, Jordan.
Neurol Res. 2021 Sep;43(9):724-735. doi: 10.1080/01616412.2021.1922182. Epub 2021 May 5.
Genetic polymorphisms of drug efflux transporters as ATP-binding cassette subfamily B, member 1 (ABCB1) have been suggested to modulate antiepileptic drugs (AEDs) response. We aimed to explore the association of ABCB1 polymorphisms and AEDs resistance among epileptic patients.
A total of 86 Jordanian epileptic patients treated with AEDs was included in the study. DNA was extracted from blood samples and genotyping and haplotypes analyses were conducted for Nine single nucleotide polymorphisms (SNPs) on the ABCB1 gene.
Data revealed that none of the examined SNPs were associated with resistance to AEDs neither on the level of alleles nor genotypes. However, strong association was found between rs2235048 (OR = 10.6; 95%CI = [1.89-59.8], = 0.01), rs1045642 (OR = 14; 95%CI = [1.3-156.7], = 0.02), rs2032582 (OR = 9.1; 95%CI = [1.4-57.3], = 0.04) and rs1128503 (OR = 18.7; 95%CI = [1.6-222.9], = 0.02), ABCB1 polymorphisms and resistance to AEDs among females but not males. Haplotype analysis revealed statistically significant associations. The strongest significant associations were for haplotypes containing 2677G_1236 T in two-SNPshaplotypes (OR = 4.2; 95%CI = [1.2-14.9], = 0.024); three-SNPs-haplotypes (OR = 4.2; 95% CI = [1.2-14.9], = 0.02); four-SNPs-haplotypes (OR = 4.1; 95%CI = [1.2-14.3], = 0.026).
Data suggests that there is a gender dependent association between ABCB1 genetic polymorphisms and response to AEDs. Additionally, ABCB1 haplotypes influence the response to AEDs. Further investigation is needed to confirm the results of this study.
药物外排转运蛋白 ATP 结合盒亚家族 B 成员 1（ABCB1）的基因多态性被认为可以调节抗癫痫药物（AEDs）的反应。我们旨在探讨癫痫患者中 ABCB1 多态性与 AED 耐药之间的关系。
本研究纳入了 86 名接受 AED 治疗的约旦癫痫患者。从血样中提取 DNA，并对 ABCB1 基因的 9 个单核苷酸多态性（SNP）进行基因分型和单倍型分析。
数据显示，在所检查的 SNP 中，无论是等位基因还是基因型水平，均与 AED 耐药无关。然而，rs2235048（OR=10.6；95%CI=[1.89-59.8]，=0.01）、rs1045642（OR=14；95%CI=[1.3-156.7]，=0.02）、rs2032582（OR=9.1；95%CI=[1.4-57.3]，=0.04）和 rs1128503（OR=18.7；95%CI=[1.6-222.9]，=0.02）与 ABCB1 多态性与女性而非男性对 AEDs 的耐药性之间存在显著关联。单倍型分析显示存在统计学显著关联。最强显著关联存在于两个 SNP 单倍型中包含 2677G_1236T 的单倍型（OR=4.2；95%CI=[1.2-14.9]，=0.024）；三个 SNP 单倍型（OR=4.2；95%CI=[1.2-14.9]，=0.02）；四个 SNP 单倍型（OR=4.1；95%CI=[1.2-14.3]，=0.026）。
数据表明，ABCB1 基因多态性与 AED 反应之间存在性别依赖性关联。此外，ABCB1 单倍型影响 AED 的反应。需要进一步的研究来证实本研究的结果。
