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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VPA单药治疗的癫痫患儿,测定其VPA稳态血药浓度。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A/A型基因的患儿。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等位基因的分布频率是30.00%,而G突变基因的分布频率为70.00%。结论:癫痫患儿UGT2B7基因的A268G突变可能改变VPA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VPA血药浓度产生影响,测定其基因型对于获得适合的VPA稳态浓度和设定起始用药剂量有积极意义。
OBJECTIVE: To evaluate the effect of UGT2B7-A268G genetic polymorphism on VPA serum concentration in VPA monotherapy in children with epilepsy. Methods: 200 children with epilepsy treated with VPA monotherapy were enrolled in this study, and their steady-state plasma concentrations of VPA were measured. A268G of UGT2B7 coding region was amplified by polymerase chain reaction (RPLF) for genotyping. The relationship between VPA serum drug concentration and gene polymorphism was analyzed according to UGT2B7 gene polymorphism. Results: The VPA serum concentrations in patients with a genotype or homozygous UGT2B7-268G mutation were significantly higher than those in children with A / A gene mutation. Due to the large differences in individual children, adjusting for VPA concentration according to age and body mass is still significantly associated with genetic polymorphism (P <0.05). The polymorphism of UGT2B7-A268G was consistent with Hardy-Weinberg equilibrium (P> 0.05). The distribution frequency of UGT2B7-268A> G allele was 30.00% while that of G mutant gene was 70.00%. CONCLUSION: A268G mutation of UGT2B7 gene in children with epilepsy may change the pharmacokinetics of VPA and is not affected by age, body weight and other factors. The genetic polymorphism of UGT2B7 has an impact on the plasma concentration of VPA in children. To determine the genotype of UGT2B7 is of positive significance for obtaining the steady-state concentration of VPA and setting the starting dosage.