| Objective: Investigate the effects of gene polymorphisms on the serum concentration of sodium valproate of epileptic children in UGT1A3 A17G、C133T、A808G、G342A、T31C 、G81A 、A477G.Explore the effects of age,gender and combination therapy on VPA blood concentration.So as to provide reference for clinical individualized administration of valproate sodium in epilepsy children.Methods: Observed the epileptic children as observation objects,who admitted to the second affiliated hospital of South China Univeity from January 2017 to December 2018.The enrolled children should meet the diagnostic criteria for epilepsy,and only take valproate monotherapy to control seizures.They are under the age of 15 years and do not suffer from central nervous system diseases.After all enrolled children received sodium valproate for 5 half-lives,and the blood concentration of sodium valproate in the patient reached steady state.Then 4ml blood of all enrolled children was collected and divided into tube A and tube B intravenously half an hour before taking the medicine.The plasma concentration of sodium valproate in tube A was determined by HPLC,and that in tube B was used for DNA extraction.The seven selected UGT1A3,A17 G,C133T,A808 G,G342A,T31 C,G81A and A477 G genes were amplified by PCR before gene sequencing.The correlation between UGT1A3 gene polymorphism and sodium valproate concentration in children with epilepsy was analyzed by statistical method.Results: A total of 109 cases were enrolled.There are 62 male children and 47 female children.The daily dose range of sodium valproate for children is 10 ~ 48.39mg/kg.The blood concentration range of sodium valproate for children is 58.08±28.80μg/ml.45 cases were selected from the enrolled children at a certain period of time,and the polymorphisms of 7 loci of UGT1A3 gene were determined of the 45 cases.No gene mutations were detected at C133 T,A808G and G342 A loci.The effects were not statistically significant the different genotypes at G81 A,A477G and A17 G loci on the standardized blood concentration of sodium valproate in children with epilepsy(P>0.05).The effect was statistically significant the different genotypes of the T31 C gene locus on the standardized blood concentration of sodium valproate in children with epilepsy(P<0.05).The wild homozygous type of the T31 C gene locus had higher standardized blood concentration of sodium valproate than the mutant-hybrid type.Conclusion:The effect was statistically significant the UGT1A3 T31 C gene polymorphism on the standardized blood concentration of sodium valproate in children with epilepsy.The effects were not statistically significant the G81 A,A477G and A17 G polymorphisms on the standardized blood concentration of sodium valproate in children with epilepsy. |
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