遗传因素与合用丙戊酸的南方癫痫患儿对拉莫三嗪疗效的相关性

Relationship between the genetic factors and lamotrigine efficacy in epileptic children received valproic acid therapy in south China

目的探讨在合用丙戊酸(VPA)的儿童癫痫患者中,年龄、性别、体重、UGT1A4 142T>G基因多态性等影响因素对拉莫三嗪(LTG)疗效的影响,并明确中国南方癫痫儿童患者LTG的有效血药浓度。方法选取2010年1月至2016年9月在广州市妇女儿童医疗中心神经内科就诊的癫痫患儿72例,均采用LTG+VPA联合治疗。采用液质联用法检测LTG的浓度,采用限制性片段长度多态性聚合酶链式反应法测定UGT1A4 142T>G的基因型。采用卡方检验、非参数检验、Logistic回归分析等探讨各影响因素与LTG疗效的相关性及有效血药浓度。结果合用VPA时,年龄越小、体重越轻,其疗效相对差。男性较女性容易获得较好疗效。UGT1A4 142T>G对LTG疗效无显著影响。合用VPA时,患儿LTG的有效血药浓度为>2μg/m L。结论年龄显著影响LTG的疗效;合用VPA时,南方癫痫患儿LTG的有效血药浓度应>2μg/m L;本研究能为中国南方癫痫儿童的个体化给药提供参考。

Objective To investigate the effect of age, gender, weight and UGT1A4 142T 〉 G gene poly- morphism on the efficacy of LTG in epileptic children treated with valproic acid, and to determine the effective se- rum concentration of LTG in children with epilepsy in south China. Methods A total of 72 pediatric patients with epilepsy received LTG and VPA treatments were enrolled in this study. Patients were treated from January 2010 to September 2016 in Guangzhou women and childrens＇ medical center. Serum concentration of LTG was measured by using the liquid chromatography-tandem mass spectrometry. UGT1A4 142T 〉 G was genotyped by the polymerase chain reaction-restriction fragment length polymorphism method. The correlations between the efficacy of LTG and age, gender, weight were analyzed by ehi-square test, non-parametric test and logistic regression analysis, respec- tively. Results The curative effect of patients who were younger and with lighter weight were relatively poor, and men were better than women in the curative effect. UGT1A4 142T 〉 G was not related with LTG efficacy. When combined with VPA, the effective serum concentration of LTG in children with epilepsy was more than 2 g/mL. Conclusion There is a good correlation between age and LTG curative effect. The effective serum concentration of LTG in children with epilepsy, who were co-treated with VPA, was more than 2 g/mL. This study provides a refer- ence for the individual administration of children with epilepsy in south China.