| Objective To detect the frequency distribution of the Glucuronosyltransferase(UGT)2B7*2 gene polymorphism in patients with epilepsy,further study on the effect of UGT2B7*2 gene polymorphism on plasma concentration of valproic acid and carbamazepine.Methods: to establish the detailed records on taking valproic acid or carbamazepine alone in patients with epilepsy,including name,gender,age,height,weight,dose,plasma concentration data.Fasting blood samples on medication of patients more than a month at early morning,determinate the plasma concentration in patients with valproic acid or carbamazepine application of chemiluminescence immunoassay,uses PCR-RFLP method to analyze gene polymorphism on UGT2B7*2.Analysis further influence of body weight index,body surface area,weight daily dose on the standard of plasma concentration through multiple linear regression.Using single factor variance analysis,chi square test and t test for statistical analysis of the test data and clear the correlation between UGT2B7*2 gene polymorphism and the standard plasma concentration.Results: 195 cases of patients with epilepsy,the occurrence frequency of UGT2B7*2 allele gene conform to the the Hardy-Weinberg equilibrium.Valproate group117 cases,the range of standardized plasma concentration is1.13~19.30 ug.kg.ml-1.mg-1,an average of 6.13±3.81 ug.kg.ml-1.mg-1,the male and the female two groups by t test P > 0.05,so we thought gender has no effects on the plasma concentration.Standard plasma concentration has been discoveried that are not related to patients' daily dose,surface area,body mass index and other indicators by multivariate linear regression analysis,P values were 0.105,0.451,0.936,and is related to the weight daily dose,plasma concentration,both P values were 0.000,further analysis that the former showed a negative correlation(r =-0.64),the latter were positively correlated(r =0.55).Sodium valproate group 117 cases,according to the characteristics of age,different dose divided into greater than or equal to 6 age group of 84 cases;9 cases for the UGT2B7*2 mutant,hybrid type in 33 cases,42 cases of wild type,three kinds ofgenotype of standard plasma concentration by single factor analysis of variance,F=4.386,P=0.016,display significant difference of standard plasma concentration between the three groups.Continue to do the two two compare,mutant and the other two groups has statistical significance(P=0.023,P=0.004).While Valproic acid sodium group is 33 patients with less than six age,including 1 cases of UGT2B7*2 mutant,heterozygous type in 14 cases,two groups of combined for 15 cases,the wild type in 18 cases,the t test t=0.077,P=0.939,no statistical significance between the two groups.Carbamazepine group 78 cases,of which 8 cases for the UGT2B7*2 mutant,30 cases of type complex,the wild type in 40 cases,the variance analysis of standard plasma concentration of the three genotype F=0.897,P=0.412,the results showed that the three groups standard plasma concentration had no significant difference.Conclusion: the experimental reaction UGT2B7*2(H268Y,802C>T)distribution characteristicsregion in patients with epilepsy,the results of the study show UGT2B7*2 gene polymorphism has an effect on the plasma concentration of sodium valproatethat with greater than or equal to 6 year old age group patients.The standard plasma concentration of T/T type patients was significantly lower than the other two groups genotype.For carbamazepine group,UGT2B7 * 2 gene polymorphism had no effect on on the standard plasma concentration. |
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