河南汉族癫癎儿童UGT1A6 A541G基因多态性与丙戊酸血药浓度相关性研究

Effect of UGTIA6 A541G genetic polymorphism on the metabolism of valproic acid in Han epileptic children from Henan

目的检测尿苷二磷酸葡糖醛酰转移酶(UGT)1A6 A541G基因多态性在汉族癫癎患儿中的分布和突变频率,探讨UGT1A6 A541G突变各基因型与丙戊酸血药浓度的关系。方法气相色谱法测定丙戊酸血药浓度,PCR-RFLP技术检测UGTIA6 A541G基因多态性,PCR扩增产物直接测序验证基因型检测方法的可靠性。结果 147例汉族癫癎患儿中UGTIA6541位点的基因型AA、AG、GG分别为76例、65例和6例。服用单位剂量(mg/kg)引起的血药浓度AA基因型患儿为3.91±1.57μg/mL,AG基因型患儿为3.59±1.39μg/mL,GG基因型患儿为3.73±1.28μg/mL。AG、GG基因型患儿血药浓度较AA基因型患儿偏低,但差异无统计学意义。结论 UGT1A6A541G基因多态性与丙戊酸的血药浓度无显著相关性,临床上个体血药浓度的差异可能是多种因素共同作用的结果 。

Objective To investigate the distribution and frequency of UGTIA6 A541G genetic polymorphism in Han epileptic children from Henan and to evaluate the effect of UGTIA6 A541G genetic polymorphism on serum concentrations of valproic acid. Methods The method of gas chromatography was used to assay serum concentrations of valproic acid. UGTIA6 A541G genetic polymorphism was screened by PCR-RFLP. Direct sequencing was used to confirm the expected sequences of each genotype. Results The genotypic frequencies of UGTIA6 A541G were as follows： AA in 76 cases, AG in 65 cases and GG in 6 cases. The mean values of serum concentrations of valproic acid in patients with A541G AA, AG and GG were 3.91 ＋ 1.57, 3.59 -＋ 1.39 and 3.73 ＋ 1.28 Ixg/mL, respectively （dose-adjusted trough concentration on a mg/kg basis）. There were no significant differences in serum concentrations of valpmic acid among the three groups. Conclusions UGT1A6 A541G gene polymorphism does not influence serum concentrations of valproie acid in Han epileptic children. Individual differences in serum concentrations of valproic acid may be attributed to many factors.