UGT2B7 C802T和G211T基因多态性对癫痫患者丙戊酸代谢的影响

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。

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

OBJECTIVE To investigate the distribution and frequency of UGT2B7 C802T and G211T genetic polymorphism in epilepsy patients and to evaluate the effects of UGT2B7 C802T and G211T genetic polymorphism on metabolism of valproic acid.METHODS Direct chemiluminescence method was used to assay serum oncentrations of valproic acid.UGT2B7 C802T and G211T 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 C802T were as follows:CC in 14 cases,CT in 46 cases and TT in 42 cases.The genotypic frequencies of UGT2B7 G211T were as follows:GG in 78 cases,GT in 23 cases and TT in 1 case.The mean values of serum concentrations of valproic acid in patients with C802T 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 G211T 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 C802T CC and CT or TT,but no significant differences between the groups with G211T GG and GT.CONCLUSION UGT2B7 C802T (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 C802T gene polymorphism.