葡萄糖醛酸转移酶UGT2B7-A268G基因多态性对癫痫儿童丙戊酸血药浓度的影响

Effect of Udp-Glucuronosyltransferase UGT2B7 Genetic Polymorphisms on Serum Valproate Concentrations in Children with Epilepsy

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 genetic polymorphisms of udp-glucuronosyltransferase UGT2B7-A268 G locus on VPA serum concentrations in children with epilepsy. Methods： The steady state plasma concentrations of VPA in 200 children with epilepsy were detected. The A268 G of UGT2B7 was identified with polymerase chain reaction. The relationship between plasma concentrations of VPA and genetic polymorphisms were analyzed according to UGT2B7 genetic polymorphisms. Results： Our data showed that patients who carried the variant UGT2B7-268 G genotypes or homozygous had significantly lower adjusted VPA concentrations than those carrying the A / A genotypes. Because of the children’s individual differences,significant correlation existed between genetic polymorphisms and VPA concentrations adjusted by age and body mass（ P〈0.05）. The genetic polymorphisms of UGT2B7 were consistent with Hardy-Weinberg（ P〉0.05）. The distribution frequency of UGT2B7 268A〉G genotypes were 30.00%,the variant of UGT2B7 268A〉G genotypes were70. 00%. Conclusion： These results suggested that the A268 G mutation of UGT2B7 gene may affect the pharmaco-kinetics of VPA in children with epilepsy,which is not potentially interfered by age and body weight. Genetic polymorphism of UGT2B7 can affect the concentration of VPA on children,it is positive significance to measure genotype for access to appropriate steady-state concentration of VPA and set the starting dose.