ABCB1 Gene Polymorphisms Are Closely Associated With Drug-Resistant Epilepsy: Evidence Based on 377 Subjects in Chinese Pediatric Patients.

IF 0.8 4区 医学 Q4 CLINICAL NEUROLOGY Clinical Neuropharmacology Pub Date : 2023-06-07 DOI:10.1097/WNF.0000000000000555
Ting Zhao, Hong-Jian Li, Jing Yu, Hui-Lan Zhang, Jie Feng, Ting-Ting Wang, Lu-Hai Yu, Yan Sun
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Abstract

Objective: P-glycoprotein plays a role in drug resistance of epileptic patients by limiting gastrointestinal absorption and brain access to antiseizure medications. This study aimed to evaluate the association between ABCB1 polymorphisms and drug resistance in epileptic pediatric patients.

Methods: Three hundred seventy-seven epileptic pediatric patients were treated with antiseizure medications and subsequently divided into the drug-responsive group (n = 256, 68%) and drug-resistant group (n = 121, 32%). The genomic DNA of patients in the different groups was extracted, followed by the determination of the ABCB1 gene polymorphisms using polymerase chain reaction-fluorescence staining in situ hybridization.

Results: Drug-resistant patients significantly exhibited a combined generalized and focal onset than drug-responsive patients (χ2 = 12.278, P < 0.001). The TT (χ2 = 5.776, P = 0.016) genotypes of G2677T and CT (χ2 = 6.165, P = 0.013) and TT (χ2 = 11.121, P = 0.001) genotypes of C3435T were significantly more frequent in drug-resistant patients than drug-responsive patients. Similarly, the GT-CT diplotype was significantly more frequent in drug-resistant patients than in drug-responsive patients.

Conclusion: Our study findings suggest that the ABCB1 G2677T and C3435T polymorphisms are significantly associated with drug resistance in epileptic patients.

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ABCB1基因多态性与耐药癫痫密切相关:基于377例中国儿科患者的证据
目的:p -糖蛋白通过限制胃肠道吸收和大脑对抗癫痫药物的获取,在癫痫患者的耐药中发挥作用。本研究旨在评估儿童癫痫患者ABCB1多态性与耐药之间的关系。方法:对377例癫痫患儿进行抗癫痫药物治疗,分为药物反应组(256例,占68%)和耐药组(121例,占32%)。提取各组患者基因组DNA,采用聚合酶链反应-荧光染色原位杂交法测定ABCB1基因多态性。结果:耐药患者的广泛性和局灶性发病明显高于耐药患者(χ2 = 12.278, P < 0.001)。G2677T基因型TT (χ2 = 5.776, P = 0.016)、CT基因型TT (χ2 = 6.165, P = 0.013)、C3435T基因型TT (χ2 = 11.121, P = 0.001)在耐药患者中明显高于耐药患者。同样,GT-CT二倍型在耐药患者中比在药物反应患者中明显更常见。结论:我们的研究结果提示ABCB1 G2677T和C3435T多态性与癫痫患者的耐药显著相关。
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来源期刊
Clinical Neuropharmacology
Clinical Neuropharmacology 医学-临床神经学
CiteScore
1.20
自引率
10.00%
发文量
63
审稿时长
6-12 weeks
期刊介绍: Clinical Neuropharmacology is a peer-reviewed journal devoted to the pharmacology of the nervous system in its broadest sense. Coverage ranges from such basic aspects as mechanisms of action, structure-activity relationships, and drug metabolism and pharmacokinetics, to practical clinical problems such as drug interactions, drug toxicity, and therapy for specific syndromes and symptoms. The journal publishes original articles and brief reports, invited and submitted reviews, and letters to the editor. A regular feature is the Patient Management Series: in-depth case presentations with clinical questions and answers.
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