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Objective To investigate the relationship between uridine diphosphate glucuronosyltransferases (UGT) 1A6 rs2070959 polymorphism and serum concentration of valproic acid (VPA) in patients with epilepsy.Methods We selected 200 cases of epilepsy patients treated in our hospital from June 2014-January 2017.All the patients were treated with VPA monotherapy ＞ 3months.When the VPA of patients reached steady state,we detected the VPA blood level.The genotypes and allele frequencies of UGT1A6 rs2070959 in 200 epilepsy patients were determined.The average standard deviation of 1-fold VPA was used as high VPA group and vice versa as low VPA group.The genotype and allele frequencies of UGT1A6 rs2070959 were compared between the two groups,and the influencing factors of VPA concentration in epileptic patients were analyzed.Results The frequencies of A genotype,AG genotype and GG genotype were 77.01％,18.39％ and 4.60％ in the high VPA group,67.26％,19.47％ and 13.27％ in the low VPA group,with no significant difference between the two groups (P ＞ 0.05);the allele G frequency in the high VPA group was significantly lower than that in the low VPA group (13.79％).The age and weight of the high VPA group were significantly higher than those of the low VPA group (P ＜ 0.05),and the gender composition of the high VPA group was not significantly different from that of the low VPA group (P ＞0.05).Logistic regression analysis showed that age and weight gain were positively correlated with VPA concentration (P ＜ 0.05),allele G expression was negatively correlated with VPA concentration (P ＜0.05).Conclusions Allele G expression at UGT1 A6 rs2070959 is associated with decreased VPA concentration in epileptic patients,which may require a higher dose of VPA.
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The increasing identification of genetic causes for epilepsy over the recent years improves the understanding of the underlying epileptog enic process,and allows for the possibility of directed therapeutic approaches.An ideal antiepileptic therapy consists of a drug which is able to influence the functional changes caused by a specific pathogenic variant.In this review,we describe the current precise medicine approaches in genetic epilepsies.Currently established or investigated precise medicine treatments include the ketogenic diet in patients with glucose transporter typel (GLUT1) deficiency,sodium channel blockers in patients with KCNQ2 mutations,and mechanistic target of rapamycin (mTOR)-inhibitors in patients with SCN2A and SCN8A mutations.These predominantly represent already available treatments that were repurposed for use in epilepsy.The development of new therapeutic agents aiming at targets identified in genetic epilepsies will advance epilepsy treatment considerably.
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Objective To explore the effect of Levetiracetam on Electrocorticogram of epileptic rats induced by lithium-Pilocarpine.Methods Sixteen SD rats were randomly divided into two groups(8 rats in each group),normal saline group and Levetiracetam group.After epileptic model was induced by lithium-Pilocarpine,lateral ventricle was administered with Levetiraeetam and saline by the same volume.The change of frequency of epileptic discharge and different brainwave proportion distribution was observed.Results Compared with normal saline group,the epileptic discharge were significantly decreased(P＜0.01)and the proportion of δ wave was enhanced,meanwhile β wave was decreased in Levetiraeetam group(P＜0.05).Conclusion Levetiracetam has the role of anti-epilepsy in acute model of epileptic rats induced by lithium-Pilocarpine.