| 摘要: |
| 目的：在丙戊酸（VPA）单药治疗的癫痫儿童中评估葡萄糖醛酸转移酶UGT2B7-A268G位点的遗传基因多态性对VPA血清浓度的影响。方法：本研究纳入200例癫痫患儿的丙戊酸血药浓度，测定VPA稳态血清浓度。对UGT2B7编码区的A268G采用聚合酶链反应（RPLF）扩增进行基因鉴定分型。根据UGT2B7基因多态性分析VPA血清药物浓度与基因多态性的关系。结果：携带变异UGT2B7-268G一个基因型或纯合基因患儿的VPA血清药物浓度显著高于携带AA基因的患儿。由于儿童个体差异较大，根据年龄、体质量调整VPA浓度后与基因多态性仍然显著关联（P<0.05）。UGT2B7-A268G的基因多态性与Hardy-Weinberg平衡一致（P>0.05），其中UGT2B7-268A>G等位基因频率分布的是30.00%，而G突变的基因分布频率为70.00%。结论：癫痫患儿UGT2B7基因的A268G突变可能改变丙戊酸的药物代谢动力学过程，并且不受年龄、体质量等因素干扰。UGT2B7的基因多态性对儿童丙戊酸血药浓度产生影响，测定其基因型对于获得适当的丙戊酸稳态浓度和设定起始用药剂量有积极意义 |
| 关键词: 儿童 丙戊酸 UGT2B7 基因多态性 药代动力学 癫痫 |
| DOI：doi:10.13407/j.cnki.jpp.1672-108X.2016.03.012 |
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| 基金项目:国家自然科学基金，项目编号81260627 |
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| Effects of UGT2B7 Genetic Polymorphisms on Serum Valproate Concentrations in Children with Epilepsy |
| ZHANG Qin1,2, TANG Hui1, LYU Xiaofeng2, LI Le1 |
| (1. Pharacy College of Shihezi University, Shihezi Xinjiang 832002, China; 2. People’s Hospital of Hebi, Hebi Henan 458030, China) |
| Abstract: |
| Objective: The study was to evaluate the effects of genetic polymorphisms of uridine diphosphate glucuronosyltransferase (UGT2B7) gene on VPA serum concentrations in children with epilepsy. Methods: The UGT2B7 268A>G in the coding regions in the 5’-upstream regions were genotyped using polymerase chain reaction amplification followed by direct automated DNA sequencing in 200 patients treated with polytherapy with VPA. Results: Our data showed that patients carrying the variant UGT2B7 268A>G genotypes or alleles had significantly lower adjusted VPA concentrations than those carrying the wild-type genotypes. These results suggest that the UGT2B7 268A>G mutations in the 5’-upstream regions of the UGT2B7 gene affect VPA pharmacokinetics, with which is potentially interfered by age, body weight, and concomitant VPA administration. Conclusion: Polymorphism of UGT2B7 the impact on children of valproic acid plasma concentrations, measured genotype for access to appropriate steady-state concentration of valproate and set the starting dose of positive significance. |
| Key words: Children Valproate UGT2B7 Polymorphism Pharmacokinetics Epilepsy |
