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目的探讨尿苷二磷酸葡萄糖醛酸转移酶1A6(UGTlA6)基因多态性对丙戊酸钠血药浓度的影响。方法选择单药服用丙戊酸钠且无肝肾功能异常的癫痫患者67例,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法分析患者的 UGT1A6基因552位点的多态性;同时应用荧光偏振免疫法(FPIA)测定患者丙戊酸钠的血药浓度。结果 67例患者中 UGT1A6的552位点基因型为 A/A,A/C 及 C/C 的例数分别40(59.7%)、24(35.8%)及3(4.5%)。A/A 组标准血药浓度均值(4.32±0.21)μg·kg·ml~(-1)·mg~(-1)和 A/C 组(3.43±0.30)μg·kg·ml~(-1)·mg~(-1)比较差异有统计学意义;含有 C 等位基因的 A/C 及 C/C 作为一组[标准血药浓度均值(3.40±0.28)μg·kg·ml~(-1)·mg~(-1)]与 A/A 组比较,其标准血药浓度均值差异具有统计学意义。结论 UGT1A6是丙戊酸钠的代谢酶,UGT1A6基因多态性可影响丙戊酸钠的代谢,UGT1A6基因552位点含有 C 等位基因的患者应用丙戊酸钠应较常规增加用药剂量。
Objective To investigate the effect of uridine diphosphate glucuronosyltransferase 1A6 (UGT1A6) gene polymorphism on plasma concentration of valproate. Methods Sixty-seven patients with epilepsy who were treated with sodium valproate and had no abnormal liver and kidney function were selected. The UGT1A6 gene 552 locus was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) The plasma concentration of sodium valproate was determined by fluorescence polarization immunoassay (FPIA). Results The genotype of UGT1A6 in 552 loci was A / A, and the number of A / C and C / C cases were 40 (59.7%), 24 (35.8%) and 3 (4.5%) respectively. The average plasma concentration of A / A group was 4.32 ± 0.21 μg · kg · ml -1 · mg -1 and 3.43 ± 0.30 μg · kg · ml -1 ) · Mg ~ (-1) were statistically significant. A / C and C / C with C allele as a group [mean standard plasma concentration (3.40 ± 0.28) μg · kg · ml ~ (-1) 1) · mg ~ (-1)] compared with the A / A group, the standard mean plasma concentration of the difference was statistically significant. CONCLUSION: UGT1A6 is the metabolizing enzyme of sodium valproate. UGT1A6 gene polymorphism can affect the metabolism of sodium valproate. Patients with UG allele at position 552 of UGT1A6 gene should be given sodium valproate conventionally to increase dosage.