UGT1A6 A541G和A552C基因多态性与丙戊酸钠血药浓度关系的研究  

Relationship between UGT1A6 A541G and A552C genetic polymorphism and plasma concentration of sodium valproate

作　　者：康卫斌 陈静静 柴栋[1] 孙艳[1] 郭代红[1] 张明华[1] 

机构地区：[1]解放军总医院临床药学实验室,北京100853

出　　处：《中华保健医学杂志》2016年第4期280-283,共4页Chinese Journal of Health Care and Medicine

基　　金：解放军总医院临床扶持基金(2014FC-TSYS-1011)

摘　　要：目的研究UGT1A6 A541G和A552C基因多态性与丙戊酸钠(VPA)血药浓度的关系。方法对129例癫痫患者体内UGT1A6基因进行检测,采用化学发光微粒子免疫检测法检测癫痫患者体内丙戊酸钠血药浓度;采用SNa Pshot技术检测丙戊酸钠代谢基因UGT1A6。结果 129例癫痫患者中UGTIA6 A541G基因型AA、AG、GG分别为55例、61例和13例。对丙戊酸钠血药浓度进行标准化处理,AA基因型患者为(3.18±1.67)μg/ml,AG基因型患者为(2.73±1.34)μg/ml,GG基因型患者为(3.24±1.70)μg/ml,UGT1A6 A541G基因型对于丙戊酸钠血药浓度差异无统计学意义(P>0.05)。UGTIA6 A552C基因型AA、AC、CC分别为61例、56例和12例,其中AA基因型患者为(3.28±1.71)μg/ml,AC基因型患者为(2.58±1.66)μg/ml,CC基因型患者为(3.21±1.81)μg/ml,UGT1A6 A552C基因型对于丙戊酸钠血药浓度差异有统计学意义(P<0.05),含有突变基因型AG和GG患者的血药浓度低于野生基因型AA患者。不同性别在UGT1A6 A541G和A552C基因分型上差异无统计学意义(P>0.05)。结论 UGTIA6 A541G基因多态性与丙戊酸钠血药浓度无显著相关性,UGTIA6 A552C基因多态性与丙戊酸钠血药浓度有显著相关性,AC基因型患者丙戊酸钠代谢较快。Objective To investigate the distribution and frequency of UGT1A6 A541 G and A552 C genetic polymorphism in epilepsy patients and to evaluate the influence of UGT1A6 A541 G and A552 C genetic polymorphism on plasma concentration of sodium valproate（VPA） in epileptic patients. Methods One hundred and twenty-nine epileptic patients were treated with sodium valproate, and chemiluminescent microparticle immunoassay（CMIA）was used to measure their plasma concentration of sodium valproate. UGT1A6 A541 G and A552 C genetic polymorphism was screened by SNap Shot minisequencing method. Results The genotypic frequencies of UGT1A6 A541 G were as follows ：AA in 55 cases,AG in 61 cases and GG in 13 cases. The mean values of plasma concentration of sodium valproate in epileptic patients with A541 G AA,AG and GG were（3.18 ± 1.67）,（2.73 ± 1.34） and（3.24 ± 1.70） μg/ml,respectively. There were no significant differences in plasma concentration of sodium valproate between the groups with A541 G AA, AG or TT（P 0.05）. The genotypic frequencies of UGT1A6 A552 C were as follows ：AA in 61 cases,AC in56 cases and CC in 12 cases. The mean values of plasma concentration of sodium valproate in epileptic patients with A552 C AA,AC and CC were（3.28 ± 1.71）,（2.58 ± 1.66） and（3.21 ± 1.81） μg/ml,respectively. There were significant differences in plasma concentration of sodium valproate between the groups with A552 C AA, AC and CC（P 0.05）. Gender had no effect on UGT1A6A541 G and A552 C genotype differences（P 0.05）. Conclusion UGT1A6 A541 G gene polymorphism dose not influence plasma concentration of sodium valproate in epileptic patients.UGT1A6 A552 C gene polymorphism is closely related with plasma concentration of sodium valproate in epileptic patients. The dosage of sodium valproate for the epileptic patients with 552 C allele in UGT1A6 should be larger than the usual dosage.

关 键 词：UGT1A6基因 基因多态性 丙戊酸钠 血药浓度 

分 类 号：R968[医药卫生—药理学]