CAJ | 학술논문

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.
목적 탐토인동난치성전(간)적진단문제급한족인동난치성전(간)MDR1기인단핵감산다태성C3435T여전(간)내약적상관성.방법 채용회고성급전첨성분석방법대400례전(간)인동진행수방,자정인동난치성전(간)(RE)진단표준,분석기중난치성전(간)류형、용약충류、용약시간、약물조정시간급료효;근거대항전(간)약물적반응장인동전(간)환자분위난치조、공제조,건강인동작위정상대조조;제취132례환인(난치조70례,공제조62례)급건강62례인동외주혈DNA,이PCR확증,DNA직접측서법검측MDR기인C3435T적단핵감산다태성;응용병례대조연구,분석기인다태성재전(간)환자중적분포특점급기여전(간)내약적상관성.결과 400례전(간)환인중난치성전(간)83례(20.8%),65례(78.3%)재6개월내완성지소2충약물조정,목전잉유42례(50.6%)동시사용3충급이상약물치료,기중6례(7.2%)동시사용4충항전(간)약물.83례난치성전(간)환자용약유효40례(48.2%),현효6례(7.2%);무효37례(44.6%),기중25례(67.6%)유불동정도적감경.70례내약조환인여62례공제조환인급62례건강대조상비교,각조CC기인형、CT기인형、TT기인형급등위기인빈솔차이균무통계학의의.다인소Logistic회귀분석현시,MDR1C3435T각기인형여전(간)내약무상관성.결론 인동전(간)환인정규치료6개월후잉불능공제발작자인위기위난치성전(간)(평균지소1차/월,>2충약물무효),다충AEDs치료잉유기필요성,미발현한족인동C3435T기인다태성여전(간)내약적상관성.
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.