Clinical Study On Relationship Between CYP2C19 Polymorphisms And VPA Induced Liver Injury In Children With Epilepsy

Objective:To investigate the relationship between the genetic polymorphisms of CYP2C19 and VPA induced liver injury in children with epilepsy, investigate the feasibility of individualized medication based on genotype.Methods:58 anticoagulant blood specimens of children with epilepsy were collected, their CYP2C19 phenotype were detected using gene chip technology.58 cases were divided into 3 groups according to their CYP2C19 phenotype:Extensive metabolizers (EMs),including 681GG-636GG, Intermediary metabolizers (IMs),including 681AA-636GG and 681GA-636GA, Poor metabolizers (PMs),including 681GA-636GA.The ALT、ALP、TBIL、GGT were tested and analysised before the VPA administration,1 month,2 months,3 months after VPA administration.Results:CYP2C19 polymorphism was found in children with epilepsy,the allele frequencies of*1/*1,*1/*2,*1/*3,*2/*2 and *2/*3 were 39.7%,44.8%,6.9%,5.1% and 3.4%; The standarized plasma concentration at steady state of VPA(mg/L) in EMs,IMs and PMs were 58.70±14.42、59.39±15.19、62.92±14.17, no statistical significance was found among each group (P>0.05).Incidence rate of VPA associated DILI in EMs,IMs and PMs were 4.3%,10% and 20%, no statistical significance was found among each group (P>0.05). Logistic regression analysis demonstrated there was no significant relationship between 3 metabolizers and DILI. Incidence rate of abnormal liver biochemical examination in EMs,IMs and PMs were 8.7%,36.7% and 60%,.The risk of incidence of abnormal liver biochemical examination in IMs and PMs were 6.079 and 15.75 times of that of EMs, the difference was statistically significant(P<0.05).Conclusion:CYP2C19 polymorphism was found in children with epilepsy. The risk of incidence rate of abnormal liver biochemical examination after VPA administration in PMs and IMs was statistically higher than that of EMs,however,there was no relationship between the genetic polymorphisms of CYP2C19 and VPA induced liver injury in children with epilepsy.Prescribing initial VPA dose and adjusting VPA dosage according to CYP2C19 phenotype is valuable in predicting VPA related DILI.