多药耐药基因MDR1 C1236T多态性在癫患儿中的分布及其与癫耐药的关系

Frequency of C1236T Polymorphism in Multidrug Resistance Gene 1 and Association of Its Polymorphisms with Multidrug-Resistant

目的研究多药耐药基因MDR1 C1236T多态性在癫患儿中的分布特点,探讨其与癫患儿对抗癫药物反应的相关性。方法收集230例癫患儿,其中对抗癫药物不敏感患儿(总耐药组)108例和敏感患儿(总敏感组)122例;选择100例健康儿童作对照;再按癫类型和病因选取耐药组和敏感组。采用PCR扩增后继以限制性内切酶片断长度分析法分别测定各组MDR1基因C1236T位点的基因型频率和等位基因频率,然后对耐药组和敏感组基因型频率和等位基因频率进行比较。结果 1.总耐药组和总敏感组患儿基因型比较和等位基因频率比较,差异均无统计学意义。2.局限性发作癫患儿中,耐药组CC基因型频率明显高于敏感组,TT基因型频率明显低于敏感组,差异均有统计学意义;耐药组C等位基因频率明显高于敏感组,T等位基因频率明显低于敏感组,差异有统计学意义;其他基因型比较差异无统计学意义。3.全面性发作癫患儿中,耐药组与敏感组基因型频率和等位基因频率比较差异均无统计学意义。4.不能确定全面和局限发作组、耐药组与敏感组基因型频率和等位基因频率比较差异均无统计学意义。5.在症状性癫患儿中,耐药组和敏感组基因型频率和等位基因频率比较差异均无统计学意义。特发性癫或隐源性癫患儿,耐药组和敏感组基因型频率和等位基因频率比较差异均无统计学意义。结论 1.C1236T位点多态性中CC基因型和C等位基因频率高可能是局限性癫患儿发生耐药的危险因素,其他类型的癫与C1236T多态性基因型和等位基因关系不大。2.MDR1 C1236T位点多态性与不同病因的癫患者对抗癫药物的反应关系不大。

Objective To determine the frequency of polymorphism at C1236T of multidrug resistance gene 1（MDR1） in epileptic patients and study the association of this polymorphism with antiepileptic drug treatment in epileptic patients.Methods Subjects were classified,of whom 108 cases were resistant to antiepileptic drug treatment（RS） and 122 cases were responsive to the treatment（RP）,and 100 healthy children were assigned as the healthy control group.Then,RS and RP were classified in all subjects by the type and cause of epilepsy.Genotypes of the C1236T polymorphism were determined by polymerase chain reactionfollowed by restriction fragment length polymorphism（RFLP）.Genotype and allele frequencies were compared between the RS group and RP group.Results 1.In all subjects,there were no significant differences both in the genotype frequency and allele frequency between the RS group and RP group.2.There were significant differences of C and T,CC and TT between the RS group and RP group.3.In the patients with generalized seizures,there were no significant differences both in the genotype frequency and allele frequency between the 2 groups.4.In the patients with unclassified generalized seizures or in partial seizures,there were no significant differences between the RS group and RP group.5.There was no significant difference between the RS group and RP group in symptomatic epileptic patients,in idiopathic epilepsy group or cryptogenic epileptic patients,and the results were the same.Conclusions 1.CC genotype and C allele frequency may be the risk factors of pharmacoresistance.It is explained that patients with partial seizure are more commonly resistant to antiepileptic drug treatment.2.There is no association between C1236T in MDR1 gene and response to antiepileptic drug treatment in Chinese patients with different etiological epilepsy and other types of epilepsy.