儿童癫癎对药物反应性与多药耐药基因MDR1C3435T多态性的相关性研究

Association of a polymorphism in MDR1 C3435T with response to antiepileptic drug treatment in ethic Han Chinese children with epilepsy

摘要:

目的:探讨汉族癫癎患儿MDR1基因单核苷酸多态性（C3435T）与对抗癫癎药物反应的相关性。方法：214例癫癎患儿根据对抗癫癎药物的反应性分为耐药组和对药物反应良好组，提取外周血基因组DNA，用PCR-RFLP的方法即多聚合酶链反应（PCR）扩增后继以限制性内切酶片断长度多态性（RFLP）分析，对不同药物反应性与基因型频率、等位基因频率结果进行分析。结果：214例可明确分型的病例中，对药物反应良好的有164例，耐药的有50例 。两组病例的等位基因频率比较和基因型频率相比较，均未发现差异有显著性。结论：该研究未能反映汉族儿童C3435T基因多态性与癫癎病例对药物反应之间的相关性。［中国当代儿科杂志，2007，9（1）：11-14］

Abstract:

OBJECTIVE: P-glycoprotein 170 (P-gp) is a plausible biologic candidate for pharmacoresistance in epilepsy. The expression and efflux efficiency of P-gp is influenced by a polymorphism (C3435T) in the encoding gene (MDR1). The CC genotype at the MDR1 C3435T polymorphism was reported to be associated with the response to antiepileptic drug treatment. This study attempted to replicate this finding by examining the association of this genetic polymorphism with response to antiepileptic drug treatment in ethnic Han Chinese children with epilepsy. METHODS: Two hundred and fourteen ethnic Han Chinese children with epilepsy were classified based on the response to antiepileptic drug treatment: drug-nonresponsive and drug-responsive. DNA samples were obtained from the patients. Genotypes of the C3435T polymorphism were determined by traditional polymerase chain reaction followed by restriction digestion (PCR-RFLP). The frequency of genotypes and alleles between the two groups was compared by Chi-square test. RESULTS: Of the 214 patients, 164 were dru-responsive and 50 were drug-nonresponsive. There were no significant differences in the allele frequency and genotype frequency between the two groups. CONCLUSIONS: There is no an association between the CC genotype or C allele at the locus of C3435T in MDR1 gene and response to antiepileptic drug treatment in ethnic Han Chinese children with epilepsy.［Chin J Contemp Pediatr, 2007, 9 (1):11-14］