摘要
目的:探讨炎症性肠病(inflammation bowel disease,IBD)患者谷胱甘肽S转移酶(glutathione-S-transferase,GST)基因多态性对硫唑嘌呤(azathioprine,AZA)活性代谢物6-硫鸟嘌呤核苷酸(6-thioguanine nucleotides,6-TGN)浓度的影响,以期为优化患者AZA治疗方案提供参考。方法:前瞻性收集接受AZA治疗的IBD患者相关临床资料,给药前采用多重PCR技术结合高通量测序技术的靶向测序法测得患者GST-A1、GST-M1、GST-P1、GST-T1基因型,并应用HPLC法测定患者红细胞中6-TGN稳态谷浓度,利用SPSS 26.0软件进行统计分析。结果:研究共纳入90例IBD患者。GSTA1、GST-M1、GST-P1、GST-T1等位基因频率均符合Hardy-Weinberg平衡定律。Logistic回归分析显示携带GST-A1突变基因是6-TGN谷浓度升高的独立危险因素(低浓度水平OR=17.50,P=0.030;高浓度水平OR=3.60,P=0.033),而GST-M1、GST-P1、GST-T1基因多态性与6-TGN浓度水平无显著相关(P>0.05)。结论:GST-A1基因多态性可影响AZA活性代谢物6-TGN浓度水平,AZA治疗前进行GST-A1基因型检测将有助于临床个体化用药。
AIM:To investigate the effects of glutathione-S-transferase(GST)gene polymorphism on the concentration of 6-thioguanine nucleotides(6-TGN),an active metabolite of azathioprine(AZA),in patients with inflammatory bowel disease(IBD),in order to provide reference for the optimization of AZA treatment in patients.METHODS:The clinical data of patients with IBD treated by AZA were collected prospectively,the genotypes of GST-A1,GST-M1,GST-P1 and GST-T1 were detected by targeted sequencing of multiplex PCR combined with high-throughput sequencing technology before administration,and the steady-state trough concentrations of 6-TGN in patients'red blood cells were determined by HPLC.Statistical analysis was carried out by SPSS 26.0 software.RESULTS:A total of 90 patients were included in this study.The alleles frequencies of GST-A1,GST-M1,GST-P1 and GST-T1 were consistent with Hardy-Weinberg equilibrium law.Logistic regression analysis showed that carrying GST-A1 mutant gene was an independent risk factor for the increase of trough concentration of 6-TGN(low concentration OR=17.50,P=0.030;high concentration OR=3.60,P=0.033),while the gene polymorphism of GST-M1,GST-P1,GST-T1 had no significant correlation with the concentration of 6-TGN(P>0.05).CONCLUSION:The gene polymorphism of GST-A1 may affect the concentration of 6-TGN,an active metabolite of AZA,and detection of GST-A1 genotype before AZA treatment will contribute to clinical individualized medication.
作者
董家珊
陈嘉睿
曾大勇
刘亦伟
许建文
林荣芳
DONG Jiashan;CHEN Jiarui;ZENG Dayong;LIU Yiwei;XU Jianwen;LIN Rongfang(Department of Pharmacy,the Second Affiliated Hospital of Xiamen Medical College,Xiamen 361021,Fujian,China;Department of Pharmacy,the First Affiliated Hospital of Fujian Medical University,Fuzhou 350005,Fujian,China)
出处
《中国临床药理学与治疗学》
北大核心
2025年第10期1383-1390,共8页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
福建省卫生健康委员会青年科研课题(2022QNA037)。
