UGT1A6、UGT1A9基因多态性对汉族癫痫患者丙戊酸血药浓度的影响

发布时间：2018-08-31 08:07

【摘要】：目的:考察尿苷二磷酸葡萄糖醛酸转移酶(UGT)1A6和1A9基因多态性对汉族癫痫患者丙戊酸血药浓度的影响。方法:选取2014年1月—2015年4月于我院门诊就诊的汉族癫痫患者107例,均使用丙戊酸单药治疗,治疗时间为3个月~6年。采用酶放大免疫法测定患者体内丙戊酸稳态血药浓度,采用基质辅助激光解吸电离飞行时间质谱法检测其UGT1A6(rs2070959、rs6759892)和UGT1A9(rs13418420、rs2741045、rs2741049、rs6731242、rs72551330)基因型,并考察基因多态性与丙戊酸标准化血药浓度(CDR)的相关性。结果:未检出UGT1A9 rs72551330突变型,其余6个位点基因型频率均符合Hardy-Weinberg平衡(P0.05)。UGT1A6 rs2070959、rs6759892突变基因携带(AG+GG或TG+GG型)者丙戊酸CDR值显著低于其野生纯合子携带(AA或TT型)者,差异均有统计学意义(P0.05);而携带UGT1A9 rs13418420、rs2741045、rs2741049和rs6731242野生纯合子和突变基因的患者丙戊酸CDR值比较,差异均无统计学意义(P0.05)。结论:汉族癫痫患者UGT1A6 rs2070959、rs6759892基因多态性与丙戊酸血药浓度有关,且UGT1A6 rs2070959、rs6759892突变基因携带者可能需要更高的丙戊酸剂量。
[Abstract]:Aim: to investigate the effect of (UGT) 1A6 and 1A9 gene polymorphisms of uridine diphosphate glucuronyltransferase (UGT) 1A6) on serum valproic acid concentration in patients with epilepsy in Han nationality. Methods: 107 Han patients with epilepsy from January 2014 to April 2015 were treated with valproic acid for 3 months to 6 years. The stable blood concentration of valproic acid in patients was determined by enzyme amplification immunoassay. The genotypes of UGT1A6 (rs2070959,rs6759892) and UGT1A9 (rs13418420,rs2741045,rs2741049,rs6731242,rs72551330) were detected by matrix assisted laser desorption ionization time of flight mass spectrometry. To investigate the relationship between gene polymorphism and valproic acid standardized serum drug concentration (CDR). Results: no UGT1A9 rs72551330 mutation was detected, and the valproic acid CDR values of the other 6 loci were significantly lower than those of the wild homozygous carriers (AA or TT). The frequencies of the other 6 loci were in line with the Hardy-Weinberg balance (P0.05). UGT1A6 rs2070959,rs6759892 mutation gene carrying (AG GG or TG GG type was significantly lower than that of the wild homozygote carriers (AA or TT). The difference was statistically significant (P0.05), while the CDR value of valproate in patients with wild homozygote and mutant gene of UGT1A9 rs13418420,rs2741045,rs2741049 and rs6731242 had no statistical significance (P0.05). Conclusion: the polymorphism of UGT1A6 rs2070959,rs6759892 gene is associated with valproic acid concentration in patients with epilepsy in Han nationality, and the carrier of UGT1A6 rs2070959,rs6759892 mutation gene may need higher valproic acid dosage.
【作者单位】：解放军第175医院药学科;
【分类号】：R971+.6;;R968

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