UGT1A6基因多态性与癫痫患者丙戊酸血药浓度相关性研究

目的：探讨尿苷二磷酸葡萄糖醛酰转移酶（UGT）1A6基因多态性对癫痫患者丙戊酸血药浓度的影响。方法：对40例癫痫患者应用限制性酶切片段多态性技术分析中国汉族人常见的UGT1A6552A＞C等位基因变异，应用荧光偏振免疫法测定患者丙戊酸的血药浓度，在进行标准化以排除剂量和体重对血药浓度的影响后，分析不同UGT1A6基因型患者丙戊酸血药浓度的差异。结果：UGT1A6552A＞C等位基因频率为0.2625，符合Hardy-Weinberg平衡。将患者分为 AA野生纯合子型慢代谢组和AC合并AA突变型快代谢组，慢代谢组的丙戊酸标准化血药浓度显著高于快代谢组（P＜0.01）。结论：UGT1A6552A＞C基因多态性与丙戊酸的血药浓度有相关性，该位点突变可导致丙戊酸血药浓度降低。

Association between Genetic Polymorphisms of UGT1A6 and Serum Valproate Concentration

To investigate the relationship between the genetic polymorphism of UGT1A6 and the serum concentration of valproate （VPA） in patients with epilepsy. Methods： The peripheral blood sam-ples of 40 patients with epilepsy were collected to undergo PCR. A PCR-RFLP method was used to exam-ine the UGT1A6 552A〉C allele. Fluorescence polarization immunoassay was used to measure the VPA serum concentration standardized by dosage and body weight. Results： The allele frequency of UGT1A6 was 0.2625 which fitted the Hardy-weinberg equilibrium. Forty patients were classified into 2 groups： ex-tensive metabolizers （EM） with the genotype of AC or CC alleles, and poor metabolizer （PM） with the ho-mozygous genotype of AA. The VPA serum concentration of the PM group was significantly higher than that of the EM group （P〈0.01）. Conclusion： The VPA serum concentration was affected by UGT1A6 552A〉C. The VPA serum concentration of the PM is significantly higher.