The Correlation Research Of UGT Genetic Polymorphism And Valproic Acid's Serum Concentration

Objectives:Establish a genotyping method of UGT2B7-268A>G to investigate its distribution features in Chinese population. Explore the effect of UGT2B7-268A> G,UGT2B7G211T gene polymorphism to valproic acid's serum drug concentration.Methods:Collect the detailed clinical information of a total of 248 epilepsy patients who took long-term use of valproic acid drugs, male 166 cases and female 82 cases.Establish a data base including basic information, epilepsy type, fit time, drug use, treatment effect, liver and kidney function and so on. Steady serum concentration were monitored from 2mL peripheral blood drawed in the morning before the patients took valproic acid,all serum concentration were standardized according to patients weight and daily doses. Genome DNA were extracted from blood cells. The genotypes of UGT2B7-268A>G and UGT2B7G211T in all subjects were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay.Statistical analyses were performed by multivariate linear regression one-way ANOVA,χ2 test and paired T-test.Results:The standardized serum concentration of 248 patients are between 132.86μg·kg·ml-1·mg-1 to 23222.50μg·kg·ml-1·mg-1.There's no significant difference between gender, age and body mass index. Daily dose according to weight and standardized serum concentration were positively correlated.The genetic polymorphisms of UGT2B7-268A>G and UGT2B7G211T genes were consistent with Hardy-Weinberg equilibrium.UGT2B7-268A>G allele frequency distribution A is 30.05%, G is 69.95%, genotype of AA. AG. GG have significant difference in serum concentration as variance analysis result showed (F =5.477, P=0.005).Further analysis of paired T test shows that, AA type has significant difference from GG type(P=0.048), serum concentration of AA type is much more higher than GG type, no significant difference between AA type and AG type, GG type and AG type either.UGT2B7 G211T allele frequency distribution G is 77.24%, T is 22.58%, genotype of GG,GT and TT have no significant difference in standardized serum concentration.Conclusion:This study reveals UGT2B7-268A>G gene polymorphism distribution in Chinese epilepsy population, the research results show that UGT2B7-268A>G might plan an important role in valproic acid's metabolism, and has certain effect to valproic acid's serum concentration, as genotype A/A is much more higher than others. Epilepsy patient with this genotype should be taken consider to adjust dose or treatment. UGT2B7 G211T gene polymorphism shows no significant difference in valproic acid's standardized serum concentration.