UGT1A6 A541G基因多态性对癫痫儿童丙戊酸钠血药谷浓度的影响  

Effect of UGT1A6 A541G genetic polymorphism on serum concentration of sodium valproate in children with epilepsy

作　　者：姜永生[1] 杨琳[1] 

机构地区：[1]西安交通大学第二附属医院儿科,陕西西安710004

出　　处：《中国妇幼健康研究》2016年第12期1526-1528,共3页Chinese Journal of Woman and Child Health Research

摘　　要：目的探讨尿苷二磷酸葡萄糖醛酸基转移酶(UGT)1A6 A541G基因多态性对丙戊酸钠血药谷浓度的影响。方法患儿服药至少5个半衰期后,丙戊酸钠血药谷浓度达到稳态时采集静脉血,全血基因组DNA提取后经PCR扩增目标基因,使用焦磷酸测序技术检测UGT1A6 A541G基因多态性,同时气相色谱法测定丙戊酸钠血药谷浓度。结果在67例患儿中,UGT1A6 A541G基因型为A/A者49例(73.1%),A/G者17例(25.4%),G/G者1例(1.5%),根据基因型分为A组(A/A者)和B组(A/G者和G/G者)。B组患儿丙戊酸钠的标准血药谷浓度均值(3.43±0.38)mg/m L较A组(4.13±0.21)mg/m L低,结果有显著统计学差异(t=2.51,P<0.05)。结论 UGT1A6 A541G基因多态性影响丙戊酸钠的代谢与排泄,提示含有UGT1A6A541G等位基因的患儿口服丙戊酸钠应高于常规用量。Objective To evaluate the effect of uridine diphosphoglucuronyl transferase（ UGT） 1A6 A541 G genetic polymorphism on serum concentration of sodium valproate. Methods Venous blood of epileptic children with serum concentration of sodium valproate reaching steady state after at least 5 half-lives was collected. Target gene was amplified by PCR after whole blood genomic DNA extraction,and UGT1A6 A541 G gene polymorphism was detected by pyrosequencing. Method of gas chromatography was used to assay serum concentration of sodium valproate. Results The genotypic frequencies of UGT1A6 A541 G were as follows： A / A in 49 cases（ 73. 1%）,A /G in 17 cases（ 25. 4%） and G / G in 1 case（ 1. 5%）. According to the genotypes of UGT1A6 A541 G the patients were divided into two groups,group A（ A / A） and group B（ A / G and G / G）. Mean value of serum concentration of sodium valproate of patients in group A（ 4. 13 ± 0. 21mg/m L） was higher than that in group B（ 3. 43 ± 0. 38mg/m L） with statistical significance（ t = 2. 51,P 〈0. 05）.Conclusion The genetic polymorphism of UGT1A6 A541 G affects metabolism and excretion of sodium valproate,which indicates that the dosage of sodium valproate for patients with UGT1A6 A541 G allele should be higher than usual.

关 键 词：UGT1A6 A541G基因多态性 丙戊酸钠 癫痫 儿童 

分 类 号：R725[医药卫生—儿科]