Effect of UGT2B7 genetic variants on serum valproic acid concentration
10.3969/j.issn.1672-7347.2013.08.002
- VernacularTitle:UGT2B7基因多态性对丙戊酸血药浓度的影响
- Author:
Hongying MA
;
Ting ZHANG
;
Zhicheng GONG
;
Boting ZHOU
;
Ming ZOU
;
Shan XIAO
;
Wu ZHU
- Publication Type:Journal Article
- Keywords:
UGT;
genetic polymorphism;
valproic acid;
epilepsy
- From:
Journal of Central South University(Medical Sciences)
2013;38(8):766-772
- CountryChina
- Language:Chinese
-
Abstract:
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,χ2 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. hTe 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 signiifcant 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%. hTere was no signiifcant difference in standardized serum concentration among genotypes of GG, GT, and TT.
Conclusion:hTis 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.
