中国药房2017，Vol.28Issue(20)：2737-2742,6.DOI:10.6039/j.issn.1001-0408.2017.20.01
根据UGT1A4142T>G基因多态性和丙戊酸血药浓度定量估算我国汉族癫痫儿童体内拉莫三嗪的血药浓度
Quantitative Estimation of Blood Concentration of Lamotrigine in Chinese Han Pediatric Patients with Epi-lepsy Based on UGT1A4142T>G Polymorphism and Blood Concentration of Valproic Acid
摘要
Abstract
OBJECTIVE:To investigate the effects of UGT1A4142T>G polymorphism and blood concentration of valproic ac-id(VPA)on blood concentration of lamotrigine(LTG)in southern Chinese Han children with epilepsy,and to establish the predic-tion equation for quantitatively estimating blood concentration of LTG. METHODS:A total of 72 southern Chinese Han children with epilepsy selected from Guangzhou Women and Children's Medical Center during Jan. 2010-Sept. 2016 were given LTG+VPA. LC-MS/MS and enzyme amplified immunoassay were adopted to determine the blood concentration of LTG and VPA. RFLP-PCR was adopted to determine UGT1A4142T>G polymorphism. The relationships of age, gender, blood concentration of VPA, UGT1A4142T>G polymorphism and LTG concentration-to-dose-ratio (CDR) were also investigate. The prediction equation for blood concentration of LTG was established by multiple linear regression analysis. RESULTS:Age and blood concentration of VPA were positively related to CDR of LTG(r=0.225,0.300,P<0.05);there was no statistical significance in the influence of gender on CDR of LTG(P>0.05). UGT1A4 TT,TG and GG genotypes were detected in 39,29,and 4 cases respectively;the frequencies of each genotype were in line with the Har-dy-Weinberg balance(P>0.05). CDR of LTG of TT genotype was significantly lower than those of TG and GG genotype,with sta-tistical significance(P<0.05). Results of multiple linear regression analysis showed that the dose of LTG(x1),body weight(x2), blood concentration of VPA(x3)and UGT1A4142T>G polymorphism(x4)were all related to blood concentration of LTG(P<0.05). Using blood concentration of LTG(c)as dependent variable,above factors as independent variable,the regression equation was c=0.794+0.032x1-0.057x2+0.010x3+0.532x4(R2=0.616,P<0.05;UGT1A4 TT genotype was equal to 0,TG and GG genotype was equal to 1). There was a strong positive correlation between predicted blood concentration and measured ones(r=0.785,P=0.001). CONCLUSIONS:The dose of LTG,body weight,blood concentration of VPA and UGT1A4142T>G polymorphism may associated with blood concentration of LTG. Established prediction equation can provide reference for precise medication in south-ern Chinese Han children with epilepsy.关键词
拉莫三嗪/丙戊酸/UGT1A4142T>G/基因多态性/南方/汉族/儿童癫痫Key words
Lamotrigine/Valproic acid/UGT1A4142T>G/Gene polymorphisms/Southern/Han population/Pediatric epi-lepsy分类
医药卫生引用本文复制引用
何艳玲,杨业春,侯连兵,和凡,莫小兰,李嘉丽,王雪丁,张杰,陈娟,温预关,尚德为..根据UGT1A4142T>G基因多态性和丙戊酸血药浓度定量估算我国汉族癫痫儿童体内拉莫三嗪的血药浓度[J].中国药房,2017,28(20):2737-2742,6.基金项目
广东省科技计划项目(No.2009B060700016) （No.2009B060700016）
