Study On The Relationship Between UGT1A6 And UGT2B7 Gene Polymorphisms And The Pharmacokinetics Of Sodium Valproate In Epilepsy Patients In Qinghai Area

Objective:nucleotide polymorphisms can alter the amino acid sequence of peptide chains at the transcriptional level and affect the function of the encoded product,the metabolic process and clearance rate of sodium valproate may be directly affected by UGT gene polymorphisms.To explore the distribution of UGT1A6 and UGT2B7 gene polymorphisms in patients with epilepsy in Qinghai area,and to compare the difference of sodium valproate concentration under different UGT genotypes.Methods:104 patients with epilepsy who were treated with sodium valproate monotherapy in Qinghai area were selected as the research object.Serum concentration of sodium valproate in patients was measured by chemiluminescence microparticle immunoassay,and the detected drug concentration was standardized by concentration-dose ratio(CDR).Polymorphism of UGT1A6*2(T19G,A541 G,A552C)and UGT2B7*2(C802T)were analyzed by dideoxy terminal termination method(Sanger method).Multiple linear regression was used to determine the association between serum valproate concentration and UGT1A6 and UGT2B7 genotypes.Results:1.Mutation frequencies of UGT1A6 and UGT2B7 in this study population were 30.29% and 40.87%,respectively.2.In UGT1A6*2 gene,the CDR value of valproate in heterozygous mutant and homozygous mutant was significantly lower than that in wild type(P = 0.002);In UGT2B7 802C>T gene,CDR of CC type and CT type was significantly higher than that of wild-type TT type,(P=0.014).Albumin was negatively correlated with CDR(r =-0.276,P = 0.005 < 0.05).3.Multiple linear regression model was established,UGT1A6,UGT2B7 and albumin still had significant effects on CDR(P < 0.05).4.In UGT1A6*2,ALT,AST,GGT and FT4 were significantly higher than heterozygous mutant(P<0.05).5.Sex,age and associated diseases(hypertension)had no significant influence on CDR(P>0.05).Conclusions:1.Among epileptic patients treated with sodium valproate monotherapy in Qinghai area,The metabolic characteristics of sodium valproate in UGT1A6*2 gene(T19G(rs6759892),A541G(rs2070959),A552C(rs1105879))wild-type patients and mutation(heterozygous mutation or homozygous mutation)patients were different,heterozygous mutation and homozygous mutation carriers metabolized faster.Individual dose adjustments may be required.2.UGT2B7*2(C802T(rs7439366))gene polymorphism was associated with the metabolism of sodium valproate in epileptic patients treated with sodium valproate monotherapy in Qinghai area.Homozygous mutant carriers had faster metabolism,which may require individual adjustment of dose.3.Serum albumin concentration may affect the concentration of sodium valproate by changing the proportion of free sodium valproate.Adverse drug reactions and drug toxicity should be warned in hypoproteinemia.