Ma Hongying, Zhang Ting, Gong Zhicheng, Zhou Boting, Zou Ming, Xiao Shan, Zhu Wu
Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008,China.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2013 Aug;38(8):766-72. doi: 10.3969/j.issn.1672-7347.2013.08.002.
To investigate the effect of UGT2B7 A268G and UGT2B7 G211T genetic polymorphism on serum drug concentration of valproic acid (VPA).
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.
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.
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.
探讨尿苷二磷酸葡萄糖醛酸基转移酶2B7（UGT2B7）A268G和UGT2B7 G211T基因多态性对丙戊酸（VPA）血清药物浓度的影响。
采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术检测248例癫痫患者UGT2B7 A268G和UGT2B7 G211T基因多态性。收集患者的基本信息、癫痫类型、用药次数和剂量、治疗反应以及肝肾功能等数据。运用SPSS 13.0软件进行多因素线性回归、单因素方差分析、χ²检验和配对t检验。
多因素线性回归分析显示，性别、年龄或体重指数与VPA之间无显著差异，但浓度-剂量比（CDRs）与VPA呈正相关。UGT2B7 A268G和UGT2B7 G211T基因多态性符合Hardy-Weinberg平衡。UGT2B7-268A>G等位基因频率分布中，A为30.05%，G为69.95%。方差分析表明，AA、AG或GG基因型的血清药物浓度存在显著差异（F=5.477，P=0.005）。配对t检验进一步分析显示，AA型与GG型有显著差异（P=0.048），AA型血清浓度显著高于GG型，而AA型与AG型、GG型与AG型之间无显著差异。UGT2B7 G211T等位基因频率分布中，G为77.24%，T为22.58%。GG、GT和TT基因型的标准化血清浓度无显著差异。
本研究揭示了中国癫痫人群中UGT2B7 A268G基因多态性分布情况。UGT2B7 A268G在VPA代谢中起重要作用，对VPA血清浓度有一定影响。具有该基因型的癫痫患者应调整VPA剂量以达到治疗效果。
