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目的 探讨儿童难治性癫(癎)的诊断问题及汉族儿童难治性癫(癎)MDR1基因单核苷酸多态性C3435T与癫(癎)耐药的相关性.方法 采用回顾性及前瞻性分析方法对400例癫(癎)儿童进行随访,自定儿童难治性癫(癎)(RE)诊断标准,分析其中难治性癫(癎)类型、用药种类、用药时间、药物调整时间及疗效;根据对抗癫(癎)药物的反应将儿童癫(癎)患者分为难治组、控制组,健康儿童作为正常对照组;提取132例患儿(难治组70例,控制组62例)及健康62例儿童外周血DNA,以PCR扩增,DNA直接测序法检测MDR基因C3435T的单核苷酸多态性;应用病例对照研究,分析基因多态性在癫(癎)患者中的分布特点及其与癫(癎)耐药的相关性.结果 400例癫(癎)患儿中难治性癫(癎)83例(20.8%),65例(78.3%)在6个月内完成至少2种药物调整,目前仍有42例(50.6%)同时使用3种及以上药物治疗,其中6例(7.2%)同时使用4种抗癫(癎)药物.83例难治性癫(癎)患者用药有效40例(48.2%),显效6例(7.2%);无效37例(44.6%),其中25例(67.6%)有不同程度的减轻.70例耐药组患儿与62例控制组患儿及62例健康对照相比较,各组CC基因型、CT基因型、TT基因型及等位基因频率差异均无统计学意义.多因素Logistic回归分析显示,MDR1C3435T各基因型与癫(癎)耐药无相关性.结论 儿童癫(癎)患儿正规治疗6个月后仍不能控制发作者认为其为难治性癫(癎)(平均至少1次/月,>2种药物无效),多种AEDs治疗仍有其必要性,未发现汉族儿童C3435T基因多态性与癫(癎)耐药的相关性.“,”Objective To discuss the diagnosis of refractory epilepsy (RE) in children, and to study the association of the single nucleotide polymorphisms (SNPs) of muhidrug-resistance gene (MDR1) C3435T with pharmaco- resistant epilepsy. Methods Four hundred children with epilepsy were retrospectively or prospectively identified from multiple sources in our hospital in Shanghai and were followed-up for the occurrence of refractory epilepsy. The clinical features of RE regarding age at onset, gender, seizure type, electroencephalogram, neuroimaging, development of central nervous system, etiology and prognosis etcetera were investigated. DNA samples were obtained from 132 patients with epilepsy (70 RE and 62 responsive epilepsy) and 62 health children by DNA extraction kit. Genotype of the C3435T polymorphism was determined by DNA sequence analysis after traditional polymerase chain reaction. The frequency of genotypes and alleles among the three groups was compared by Chi-square test. Results Eighty-three (20.8%) out of total 400 patients were RE. Among them 65 (78.3%) patients failed at least 2 drugs in six months. Forty-two (50.6%) were administered at least 3 drugs on the last follow-up. Medical treatment showed remarkable effective in 6 (7.2%) RE patients, effective in 40 RE patients (48.2%). No effectiveness was seen in another 37 (44.6%) RE patients, however 25 out of 37 presented symptomatic alleviation. Significant difference in genotype (CC, CT, Tr) frequency was neither found between RE and responsive epilepsy patients nor between RE patients and healthy controls. No association between the C3435T polymorphism in the human MDR1 gene and refractory epilepsy was found by logistic analysis. Conclusions Refractory epilepsy could be diagnosed in 6 months after being treated with anti-epilepsy drugs (AEDs) in children with average attack once per month at least and failed more than 2 AEDs. Multiple AEDs were necessary for treatment. No association between the C3435T polymorphism in the human MDR1 gene and refractory epilepsy was found by logistic analysis in this study.