多个癫痫相关基因多态性与拉莫三嗪治疗儿童癫痫血药浓度的相关性

目的 拉莫三嗪是儿童癫痫的一线治疗药物,其血药浓度与临床疗效个体差异较大,药效学和药动学通路多个相关基因突变可能是个体差异大的原因,本研究探讨代谢酶UGT1A4,转运体OCT1与ABCB1,受体SCN1A基因多态性与拉莫三嗪治疗儿童癫痫稳态血药浓度的相关性.方法 于2018年1月-2019年6月纳入杭州市第一人民医院单...

Correlation between multiple epilepsy related gene polymorphisms and serum concentrations of lamotrigine in the treatment of epilepsy in children

Objective To evaluated that association between UGT1 A4,OCT1,ABCB1 and SCN1 A polymorphisms and blood concentration of lamotrigine in pediatric epilepsy patients.Methods A total of 49 pediatric epilepsy patients treated with lamotrigine alone in Hangzhou First People’s Hospital were enrolled from January 2018 to June 2019.Steady-state plasma concentrations of lamotrigine were collected for a stable dose of consecutive 7 days and above.High performance liquid chromatography was used to measure blood concentrations of lamotrigine.Collect whole blood and analyzed the metabolic enzymes UGT1 A4(rs2011425),transporter OCT1(rs628031),ABCB1(rs1045642 and rs1128503)and receptor SCN1 A(rs3812718)gene polymorphisms by direct sequencing.The correlation between different genotypes and the dose-normalized blood concentration of lamotrigine[the blood concentration of lamotrigine divided by the daily dose and the patient’s body weight per kilogram,Concentration-to-dose-ratio by body weight,CDR,(μg/mL)/(mg/kg)]were investigated by using Kruskal-Wallis H test or Mann-Whitney U test.P<0.05 was considered statistically significant.Results There was significant associations between OCT1 rs628031 polymorphism and lamotrigine CDR,compared with AA and AG genotypes,GG genotype of OCT1 rs628031 was associated with lower LTG CDR[AA+AG vs.GG:1.27(1.03,2.20)and 0.69(0.57,1.02),P=0.002].No associations were detected between other genotypes and lamotrigine CDR.Conclusion OCT1 rs628031 polymorphisms maybe an important factor for the inter-individual in blood concentration and clinical efficacy of lamotrigine.