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.

Objective To investigate the effect of age,gender,weight and UGT1A4142T>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. UGT1A4142T > 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 chi-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. UGT1A4142T > 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.