ABCB1基因多态性与抗癫药物疗效的相关性研究  

Association between ABCB1 Polymorphisms and Response of Antiepileptic Drugs in People with Epilepsy

作　　者：吴冬燕[1] 丁玎[1] 张庆[2] 王太平 葛炎[1] 王剑虹[1] 虞培敏[1] 洪震[1] 

机构地区：[1]复旦大学附属华山医院神经内科,200040 [2]宁夏医科大学总医院神经内科,750004 [3]山西省晋城市急救中心,048000

出　　处：《中国临床神经科学》2016年第4期390-398,共9页Chinese Journal of Clinical Neurosciences

基　　金：国家自然科学基金项目(编号:81271443)

摘　　要：目的观察多药耐药基因ABCB1多态性在癫患者中的分布特点,并探讨其与癫耐药的相关性。方法采用流行病学方法收集正规服用抗癫药(AEDs)且依从性好的癫患者852例(癫组),分析其临床特点;同期选取相同地区的非癫者1 003例为对照(对照组)。癫组再分为耐药亚组(671例,服用3种或3种以上AEDs,癫发作次数在随访前1年仍≥1次)和控制亚组(181例,AEDs治疗,随访前1年无癫发作)。利用Mass ARRAY时间飞行质谱技术检测癫组和对照组ABCB1基因C3435T、G2677T/A和C1236T位点的单核苷酸多态性(SNPs)。应用分子流行病学方法,与对照组比较,分析ABCB1基因多态性在癫患者中的分布特点及对AEDs疗效的关系。结果对耐药亚组、控制亚组和对照组进行ABCB1基因多态性检测发现3组的SNPs均服从Hardy-Weinberg遗传平衡。癫组与对照组ABCB1基因C3435T、G2677T/A和C1236T位点的SNPs基因型分布差异无显著性(P>0.05);耐药亚组和控制亚组3个位点SNPs基因型分布差异无显著性(P>0.05)。单体型分析显示癫组和对照组、耐药亚组和控制亚组3个位点SNPs组成的常见单体型分布差异无显著性(P>0.05)。耐药相关的多因素Logistic回归分析未发现ABCB1基因C3435T、G2677T/A和C1236T位点SNPs与耐药有统计学意义(P>0.05)。结论未发现ABCB1基因C3435T,G2677T/A和C1236T位点多态性与AEDs耐药有相关性。Aim To determine the frequencies of polymorphisms in ATP-binding cassette subfamily B member l（ABCB1） and explore the association of these polymorphisms with pharmacoresistance in people with epilepsy. Methods Demographic and clinical information were collected and analyzed in 852 epileptic patients（epilepsy group） with good adherence under the regular anti-epileptic drugs（AEDs）treatment through epidemiological method. The control group of 1003 people without epilepsy were collected from the same areas. Depending on their response to AEDs, epilepsy group was divided into drug-resistant subgroup（852 patients, one or more seizuresper year despite 3 or more AEDs at maximally tolerated doses） and drug-responsive subgroup（seizure free for the previous year）. Mass ARRAY was employed to detect single-nucleotide polymorphisms（SNPs） of C3435 T,G2677T/A and C1236 T of ABCB1 in epilepsy group and the control group. With the retrospective case-control study method, the frequencies of these polymorphisms and association of them with multidrug-resistant epilepsy were analyzed. Results Three SNPs in drug-resistant and drug-responsive subgroups and the control group all obeyed Hardy-Weinberg equilibrium. No significant difference was found in the genotype frequencies of three SNPs between epilepsy group and the control group, nor between drug-resistant and drug-responsive subgroups（P0.05）. There was no significant difference in the haplotype frequencies between the epilepsy group and the control group（P0.05）, neither between drug-resistant and drug-responsive subgroups（P0.05）. No significant association was found between the three SNPs and pharmacoresistance（P0.05） by multivariate Logistic regressior analysis. Conclusion No association was found between ABCB1 gene C3435 T,G2677T/A and C1236 T polymorphisms and pharmacoresistance.

关 键 词：癫 抗癫药物 多药耐药 ABCB1 单核苷酸多态性 基因型 单体型 

分 类 号：R742.1[医药卫生—神经病学与精神病学]