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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 detect the distribution and mutation frequency of UGT2B7 C802T and G211T alleles in patients with epilepsy and to investigate the effects of UGT2B7 C802T and G211T genotypes on valproate metabolism in patients with epilepsy. Methods: The plasma concentration of valproic acid was determined by direct chemiluminescence and the polymorphism of UGT2B7 C802T and G211T was detected by PCR-RFLP. The reliability of genotyping assay was verified by direct sequencing of PCR amplification products. Results: Of 102 epilepsy patients, 14 were wild-type CC in UGT2B7 C802T locus, 46 and 42 were heterozygous and homozygous mutant CT, respectively. Wild type GG78 in UGT2B7 G211T locus, mutant GT, TT were 23 cases and 1 case respectively. The blood concentration of the patients with genotype 802CC genotype was (3.02 ± 1.32) μg · kg · ml-1 · mg-1 after taking the unit dose (mg · kg-1) (2.11 ± 1.26) μg · kg · ml-1 · mg-1 in genotype patients and (2.31 ± 1.25) μg · kg · ml-1 · mg-1 in TT genotypes. Serum concentrations of CT and TT Compared with CC patients was significantly lower, the difference was statistically significant. (2.28 ± 1.32) μg · kg · ml-1 · mg-1 in unit dose (mg · kg-1) of patients with genotype 211GG and (2.30 ± 1.38) μg in GT genotype · Kg · ml-1 · mg-1, there was no significant difference between GG and GT patients. CONCLUSION: There is a significant correlation between UGT2B7 C802T gene polymorphism and valproic acid plasma concentration. There is no significant correlation between UGT2B7 G211T gene polymorphism and plasma valproic acid concentration. Clinical differences in individual plasma concentrations may be related to UGT2B7 C802T gene polymorphism.