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目的研究钠离子通道基因SCN1A、SCN2A及转运体基因MDR1、SLC22A1对癫痫患儿拉莫三嗪血药浓度的影响。方法收集213例用拉莫三嗪联合丙戊酸钠治疗的癫痫患儿血样,分别用HPLC法和荧光偏振免疫分析法测定拉莫三嗪和丙戊酸浓度,用聚合酶链式反应-限制性片段长度多态性分析法及直接测序法对SCN1A(rs3812718)、SCN2A(rs17183814)、MDR1(rs1128503、rs2032582、rs1045642)与SLC22A1(rs2282413)进行基因分型,比较不同基因型对拉莫三嗪血药浓度的影响,用多元线性回归分析影响拉莫三嗪血药浓度的因素。结果 SCN1A rs3812718中GG、GA、AA患儿的拉莫三嗪标准化血药浓度分别为2.43,2.11,2.31μg·m L~(-1)·mg~(-1)·kg;SCN2A rs17183814中GG、GA、AA患儿的拉莫三嗪标准化血药浓度分别为2.68,2.20,2.17μg·m L~(-1)·mg~(-1)·kg;MDR1 rs1128503中CC、TC、TT患儿的拉莫三嗪标准化血药浓度分别为2.19,2.47,2.21μg·m L~(-1)·mg~(-1)·kg;MDR1 rs2032582中GG、GT+GA+AT、AA+TT患儿的拉莫三嗪标准化血药浓度分别为2.47,2.13,2.37μg·m L~(-1)·mg~(-1)·kg;MDR1 rs1045642中CC、CT、TT患儿的拉莫三嗪标准化血药浓度分别为2.19,2.23,2.21μg·m L~(-1)·mg~(-1)·kg;SLC22A1 rs2282413中CC、CT、TT患儿的拉莫三嗪标准化血药浓度分别为2.31,2.19,2.30μg·m L~(-1)·mg~(-1)·kg,差异均无统计学意义(P>0.05)。患儿的性别、体重、拉莫三嗪剂量以及丙戊酸均能显著性影响拉莫三嗪血药浓度(P<0.05)。结论钠离子通道基因SCN1A、SCN2A和转运体基因MDR1、SLC22A1对拉莫三嗪血药浓度无显著性影响。
Objective To study the effects of sodium ion channel gene SCN1A, SCN2A and transporter genes MDR1 and SLC22A1 on lamotrigine in children with epilepsy. Methods Totally 213 blood samples of children with epilepsy treated with lamotrigine and valproate were collected. The concentrations of lamotrigine and valproic acid were determined by HPLC and fluorescence polarization immunoassay, respectively. Polymerase chain reaction-restriction The genotypes of SCN1A (rs3812718), SCN2A (rs17183814), MDR1 (rs1128503, rs2032582, rs1045642) and SLC22A1 (rs2282413) were genotyped by the fragment length polymorphism analysis and direct sequencing. The influence of blood concentration, using multiple linear regression analysis of the factors that affect the concentration of lamotrigine plasma. Results The normalized plasma concentration of lamotrigine in children with GG, GA and AA in SCN1A rs3812718 were 2.43, 2.11 and 2.31μg · m L -1 · mg -1 · kg -1, respectively. The GG concentrations in SCN2A rs17183814 , And the standard plasma concentrations of lamotrigine in children with GA and AA were 2.68, 2.20 and 2.17 μg · m L -1 · mg -1 · kg -1, respectively. CC, TC and TT in MDR1 rs1128503 The standard plasma concentration of lamotrigine in children was 2.19,2.47,2.21μg · m L -1 · mg -1 · kg -1. The GG, GT + GA + AT, AA + TT in MDR1 rs2032582 The standard plasma concentrations of lamotrigine in children were 2.47,2.13,2.37μg · m L -1 · mg -1 · kg -1, respectively. The lamses of children with CC, CT and TT in MDR1 rs1045642 The normalized plasma concentrations of triazine were 2.19,2.23,2.21μg · m L -1 · mg -1 · kg -1, respectively. The lamotrigine-standardized plasma levels of CCLC, CT and TT in SLC22A1 rs2282413 The concentrations were 2.31, 2.19 and 2.30 μg · m L -1 · mg -1 · kg -1, respectively, with no significant difference (P> 0.05). Children’s sex, weight, lamotrigine dosage and valproic acid could significantly affect lamotrigine plasma concentration (P <0.05). Conclusion Sodium ion channel genes SCN1A, SCN2A and transporter genes MDR1 and SLC22A1 have no significant effect on the plasma concentration of lamotrigine.