多药耐药基因1 C3435T和C1236T多态性与癫痫患者苯巴比妥血清药物浓度的关系

Association of C3435T and C1236T polymorphisms in MDR1 gene with serum concentrations of phenobarbital with epilepsy

目的以中国汉族癫痫儿童为研究对象,探讨多药耐药基因1(MDR1)基因C3435T和C1236T多态性对抗癫痫药苯巴比妥药物浓度的影响。方法符合癫痫诊断标准的癫痫患者90例,服用苯巴比妥,抽取受试者外周静脉血,采用PCR-限制性片段长度多态性方法对服用苯巴比妥癫痫患者进行MDR1基因C3435T和C1236T分型,同时采用荧光偏振免疫法测定苯巴比妥的血清浓度,比较不同基因型间苯巴比妥(PB)血清浓度差异。结果 MDR1基因C3435T多态性中,PB在基因型CT、CC和TT基因型中血清浓度分别为7.02±0.89μg·m L-1,8.12±1.0μg·m L-1,6.32±0.78μg·m L-1;3基因型间差异无统计学意义(P>0.05)。MDR1基因C1236T多态性中,苯巴比妥在CT、CC和TT基因型血清浓度分别6.72±0.91μg·m L-1,7.13±0.8μg·m L-1,8.2±0.63μg·m L-1;3基因型间差异无统计学意义(P>0.05)。结论 MDR1基因C3435T和C1236T多态性不影响抗癫痫药苯巴比妥药物浓度。

Objective To evaluate the relationship between multidrug resistance gene 1（MDR1）C3435T and T1236T polymorphism and whole blood concentration of phenobarbital in epilepsy.Methods Blood samples were collected from 90 epilepsy patients,who had been treated with phenobarbital for more than 2 months to 6 years. Genotypes of the C3435T and C1236T polymorphism were determined by polymerase chain reaction（PCR）followed by restriction fragment length polymorphism （ RFLP ） .phenobarbital concentrations were measured using a fluorescence polarization immunoassay. The patients were divided into 3 subgroups for every position：GG, GT, and TT in C3435T;CC, CT, and TT in C1236T.Results Of the patients who received phenobarbital, The serum phenobarbital concentrations of the patients with CT,CC and CT genotypes in C3435T were7.02±0.89μg· mL-1 ,8.12 ±1.0μg · mL-1 , 6.32 ±0.78μg · mL-1 respectively, and there was no significant difference between the C3435T genotypes.The serum phenobarbital concentrations of the patients with CT, CC and CT genotypes in C1236T were 6.72±0.91μg· mL-1 ,7.13±0.8μg· mL-1 ,8.2±0.63μg/· mL-1 ,respectively.and there was no significant difference between the C1236T genotypes.Conclusion The MDR1 gene polymorphism is not correlated with the blood concentration of phenobarbital.