UGT2B7 C802T和G211T基因多态性对癫痫患者丙戊酸代谢的影响

Effects of UGT2B7 C802T and G211T genetic polymorphism on metabolism of valproic acid in epilepsy patients

目的:检测尿苷二磷酸葡糖醛酰转移酶UGT2B7 C802T和G211T等位基因在癫痫患者中的分布和突变频率,探讨UGT2B7 C802T和G211T基因型对癫痫患者丙戊酸代谢的影响。方法:直接化学发光法测定丙戊酸血药浓度,PCR-RFLP技术检测UGT2B7 C802T和G211T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:102例癫痫患者中UGT2B7 C802T位点野生型CC14例,杂合突变型和纯合突变型CT、TT分别为46例和42例;UGT2B7 G211T位点的野生型GG78例,突变型GT、TT分别为23例和1例;位点802CC野生基因型患者服用单位剂量(mg·kg-1)后的血药浓度为(3.02±1.32)μg·kg·ml-1·mg-1,CT基因型患者为(2.11±1.26)μg·kg·ml-1·mg-1,TT基因型患者为(2.31±1.25)μg·kg·ml-1·mg-1,CT、TT患者血药浓度较CC患者明显偏低,差异有统计学意义。位点211GG基因型患者服用单位剂量(mg·kg-1)引起的血药浓度为(2.28±1.32)μg·kg·ml-1·mg-1,GT基因型患者为(2.30±1.38)μg·kg·ml-1·mg-1,GG型与GT型患者间无统计学差异。结论:UGT2B7 C802T基因多态性与丙戊酸的血药浓度有显著相关性,UGT2B7 G211T位点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与UGT2B7 C802T基因多态性有关。

OBJECTIVE To investigate the distribution and frequency of UGT2B7 C802 T and G211 T genetic polymorphism in epilepsy patients and to evaluate the effects of UGT2B7 C802 T and G211 T genetic polymorphism on metabolism of valproic acid.METHODS Direct chemiluminescence method was used to assay serum oncentrations of valproic acid.UGT2B7 C802 T and G211 T genetic polymorphism was screened by PCR-RFLP.Direct sequencing method was used to confirm the expected sequences of each genotype.RESULTS The genotypic frequencies of UGT2B7 C802 T were as follows：CC in 14 cases,CT in 46 cases and TT in42 cases.The genotypic frequencies of UGT2B7 G211 T were as follows：GG in78 cases,GT in23 cases and TT in 1 case.The mean values of serum concentrations of valproic acid in patients with C802 T CC,CT and TT were（3.02±1.32）,（2.11±1.26）,（2.31±1.25）μg·kg·ml^-1·mg^-1,respectively.The mean values of serum concentrations of valproic acid in patients with G211 T GG,GT were（2.28±1.32）,（2.303±1.38）μg·kg·ml^-1·mg^-1,respectively（all dose adjusted trough concentration in mg·kg^-1）.There were significant differences in serum concentrations of valproic acid between the groups with C802 T CC and CT or TT,but no significant differences between the groups with G211 T GG and GT.CONCLUSION UGT2B7C802T（not UGT2B7 G211T）gene polymorphism is closely related with serum concentrations of valproic acid in epilepsy patients.The individual difference of serum concentration mau be correlated with UGT2B7 C802 T gene polymorphism.