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目的探讨多药耐药基因1(MDR1)C3435T和C1236T多态性与抗癫痫药(AEDs)血药浓度的关系。方法 2009年1月至2010年7月山东大学齐鲁儿童医院和山东大学齐鲁医院儿科门诊长期随访或住院治疗的癫痫患儿184例,服药205例次,其中服用丙戊酸钠(VPA)者110例次、服卡马西平(CBZ)者95例次,采用聚合酶链反应(PCR)和限制性内切片段多态性(RFLP)的方法对服用VPA和CBZ患儿进行MDR1基因C3435T和C1236T分型。采用荧光偏振免疫法测定患者抗癫痫药血药浓度。比较不同基因型间VPA或CBZ血药浓度差异。结果 MDR1基因C3435T多态性中,VPA组基因型CT、CC和TT患者校正后血药浓度分别为(4.17±1.99)、(5.16±2.62)、(4.78±1.72)mg/L,3基因型间差异无统计学意义(P>0.05);CBZ组的CT、CC和TT患者校正后血药浓度分别为(0.72±0.44)、(0.69±0.29)、(0.57±0.43)mg/L,3基因型间差异无统计学意义(P>0.05)。MDR1基因C1236T多态性中,VPA组的CT、CC和TT患者校正后血药浓度分别(3.73±1.48)、(5.35±2.61)、(5.71±2.40)mg/L,3基因型间差异无统计学意义(P>0.05);CBZ组的CT、CC和TT患者校正后血药浓度分别为(0.98±0.44)、(0.78±0.13)、(0.71±0.33)mg/L,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VPA和CBZ血药浓度。
Objective To investigate the relationship between multidrug resistance gene 1 (MDR1) C3435T and C1236T polymorphisms and plasma concentrations of antiepileptic drugs (AEDs). Methods From January 2009 to July 2010, 184 children with epilepsy were enrolled in Qilu Children’s Hospital of Shandong University and Qilu Hospital of Shandong University. Totally 184 children were treated with VPA In this study, 95 cases of carbamazepine (CBZ) were administered to children with VPA and CBZ for polymerase chain reaction (PCR) and restriction endonuclease polymorphism (RFLP) for MDR1 C3435T and C1236T Type. Fluorescence polarization immunoassay was used to determine the antiepileptic drug concentration in patients. The differences of plasma concentration of VPA or CBZ between different genotypes were compared. Results In the C3435T polymorphism of MDR1 gene, the corrected plasma concentrations of VPA genotype CT, CC and TT patients were (4.17 ± 1.99), (5.16 ± 2.62) and (4.78 ± 1.72) mg / L, respectively (0.72 ± 0.44), (0.69 ± 0.29) and (0.57 ± 0.43) mg / L respectively in CTZ, CC and TT patients in CBZ group (P <0.05). There was no significant difference between the two groups There was no significant difference between genotypes (P> 0.05). Among the C1236T polymorphisms in MDR1 gene, the corrected plasma concentrations of CT, CC and TT in VPA group were (3.73 ± 1.48), (5.35 ± 2.61) and (5.71 ± 2.40) mg / L, respectively (0.98 ± 0.44), (0.78 ± 0.13) and (0.71 ± 0.33) mg / L respectively in CBZ group (P> 0.05) The difference was not statistically significant (P> 0.05). Conclusion MDR1 gene C3435T and C1236T polymorphisms do not affect the antiepileptic drugs VPA and CBZ plasma concentrations.