Effect of UGT2B7 genetic variants on serum valproic acid concentration.

OBJECTIVE: To investigate the effect of UGT2B7 A268G and UGT2B7 G211T genetic polymorphism on serum drug concentration of valproic acid (VPA).

METHODS: Genetic polymorphisms of UGT2B7 A268G and UGT2B7 G211T were tested in 248 epileptic patients by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Data including basic information, epilepsy type, times and doses of drug, treatment response and liver and kidney functions were collected. Statistical analysis was performed by SPSS 13.0 through multivariate linear regression, one-way ANOVA, χ(2) test, and paired T-test.

RESULTS: Based on multivariate linear regression, there was no significant difference between gender, age, or body mass index and VPA, but concentration-to-dose ratios (CDRs) were positively correlated with VPA. The genetic polymorphisms of UGT2B7 A268G and UGT2B7 G211T were consistent with Hardy-Weinberg equilibrium. UGT2B7-268A > G allele frequency distribution A was 30.05%, and G was 69.95%. Variance analysis showed that serum drug concentration was significantly different in the genotype of AA, AG, or GG (F=5.477, P=0.005). Further analysis of paired T test showed that AA type was significantly different from GG type (P=0.048), and that serum concentration of AA type was much higher than that of GG type, while no significant difference between AA type and AG type, GG type and AG type. UGT2B7 G211T allele frequency distribution G was 77.24%, and T was 22.58%. There was no significant difference in standardized serum concentration among genotypes of GG, GT, and TT.

CONCLUSION: This study reveals UGT2B7 A268G genetic polymorphism distribution in Chinese epilepsy population. UGT2B7 A268G plays an important role in VPA's metabolism, and has certain effect on VPA's serum concentration. Epilepsy patient with this genotype should be adjusted the dose of VPA to make a therapeutic effect.