钠离子通道基因与转运体基因多态性对拉莫三嗪血药浓度的影响  

Influences of sodium channel gene and transporter gene polymorphisms on lamotrigine concentration

作　　者：陈亚南[1] 徐善森 邱枫[1] 肇丽梅[1] 

机构地区：[1]中国医科大学附属盛京医院药学部,沈阳110004

出　　处：《中国临床药理学杂志》2016年第22期2069-2072,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(81302857)

摘　　要：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 channel genes SCN1A, SCN2A, and transporter genes MDR1, SLC22A1 on lamotrigine （LTG） concentrations in epileptic children. Methods A number of 213 epileptic children treated with LTG co - administered valproic acid （VPA） were recruited. The concentrations of LTG and VPA were mea- sured in blood samples by HPLC and fluorescence polarization immunoa- ssay （FPIA）, respectively. PCR - RFLP and direct sequencing were applied to clarify the genotypes of SCN1A （rs3812718）, SCN2A （rs17183814）, MDR1 （ rs1128503, rs2032582, rs1045642） and SLC22A1 （rs2282413）, and the association between different genotypes and lamotrigine concentrations were analyzed. Multiple linear regression models were performed to detect factors on LTG concentrations.Results The LTG concentration to dose ratio （CDRLTG ）values in epileptic children with GG, GA, AA genotypes of SCN1A rs3812718 were 2.43, 2. 11, 2.31 μg . mL-1 . mg-1 . kg, respectively; CDRLTG values in epileptic children with GG, GA, AA genotypes of SCN2A rs17183814 were 2.68, 2. 20, 2. 17 μg . mL-1 . mg-1. kg, respectively; CDRLTG values in epileptic children with CC, TC, TT genotypes of MDR1 rs1129503 were 2. 19, 2.47, 2.21 μg . mL-1. mg-1. kg, respectively; CDRLTG values in epileptic children with GG, GT ＋ GA ＋ AT, AA ＋ TT genotypes of MDR1 rs2032582 were 2.47, 2. 13,2. 37 μg. mL-1. mg-1 . kg, respectively; CDRLTG values in epileptic children with GG, GT ＋ GA ＋ AT, AA ＋TT genotypes of MDR1 rs2032582 were 2. 47, 2. 13, 2. 37 μg. mL-1. mg-1. kg, respectively ; CDRLTo values in epileptic children with CC, CT, TF genotypes of MDR1 rs1045642 were 2. 19, 2. 23, 2.21 μg . mL-1. mg-1. kg, respectively; And CDRLTG values in epileptic children with CC, CT, TT genotypes of SLC22A1 rs2282413 were 2.31, 2. 19, 2.30 μg. mL-1. mg-1. kg, respectively. There were no significant differences of SCN1A, SCN2A, MDR1 and SLC22A1 single nucleotide polymorphisms （SNPs） on concentration to ratio of LTG （P 〉 0.

关 键 词：拉莫三嗪 钠离子通道基因 转运体基因 丙戊酸 血药浓度 

分 类 号：R971.6[医药卫生—药品]