周守宁, 覃利, 刘思, 刘龙山, 张亦舒, 张桓熙, 王长希, 黄民, 李嘉丽. IMPDH1基因多态性与肾移植患者麦考酚酸类药物药效学的相关性分析J. 药学学报, 2018,53(5): 765-770. doi: 10.16438/j.0513-4870.2018-0050
引用本文: 周守宁, 覃利, 刘思, 刘龙山, 张亦舒, 张桓熙, 王长希, 黄民, 李嘉丽. IMPDH1基因多态性与肾移植患者麦考酚酸类药物药效学的相关性分析J. 药学学报, 2018,53(5): 765-770. doi: 10.16438/j.0513-4870.2018-0050
ZHOU Shou-ning, QIN Li, LIU Si, LIU Long-shan, ZHANG Yi-shu, ZHANG Huan-xi, WANG Chang-xi, HUANG Min, LI Jia-li. Associations of IMPDH1 polymorphisms with pharmacodynamics of mycophenolic acid in renal transplant patientsJ. Acta Pharmaceutica Sinica, 2018,53(5): 765-770. doi: 10.16438/j.0513-4870.2018-0050
Citation: ZHOU Shou-ning, QIN Li, LIU Si, LIU Long-shan, ZHANG Yi-shu, ZHANG Huan-xi, WANG Chang-xi, HUANG Min, LI Jia-li. Associations of IMPDH1 polymorphisms with pharmacodynamics of mycophenolic acid in renal transplant patientsJ. Acta Pharmaceutica Sinica, 2018,53(5): 765-770. doi: 10.16438/j.0513-4870.2018-0050

IMPDH1基因多态性与肾移植患者麦考酚酸类药物药效学的相关性分析

Associations of IMPDH1 polymorphisms with pharmacodynamics of mycophenolic acid in renal transplant patients

  • 摘要: 探讨IMPDH1基因多态性对肾移植患者麦考酚酸类药物药效学的影响。纳入315例肾移植术后进行三联免疫疗法(麦考酚酸类药物+他克莫司+泼尼松)的患者。采用Agena MassARRAY®方法检测患者IMPDH1基因型。通过高效液相色谱法检测术后稳定期患者麦考酚酸(MPA)及其主要代谢物麦考酚酸葡萄糖苷酸(MPAG)的血浆药物浓度。应用SPSS 21.0软件对IMPDH1基因多态性(rs10954183、rs12536006、rs13242340、rs2278293、rs2288549)与肾移植患者排斥、术后感染等指标的相关性进行分析。结果显示,IMPDH1 rs2288549 AG型是肾移植患者术后出现急性排斥反应的危险因素(OR=6.629,P<0.05);IMPDH1 rs2278293 CT型是肾移植患者术后出现感染的危险因素(OR=2.812,P<0.05)。以上研究表明,IMPDH1 rs2288549是肾移植患者术后出现急性排斥反应的影响因素,IMPDH1 rs2278293是肾移植患者术后出现感染的影响因素,上述SNP可作为参考优化临床用药方案,提高疗效,降低不良反应的发生率。

     

    Abstract: The study was designed to investigate the effect of IMPDH1 gene polymorphism on the pharmacodynamics of mycophenolic acid in the renal transplant patients. 315 patients with renal transplantation were treated with triple immunotherapy (mycophenolic acid + tacrolimus + prednisone). The Agena MassARRAY assay was used to detect the IMPDH1 genotypes in patients above. The plasma drug concentration of mycophenolic acid (MPA) and its main metabolite mycophenolic acid glucuronide (MPAG) was detected by high performance liquid chromatography (HPLC). The correlation between IMPDH1 gene polymorphism (rs10954183, rs12536006, rs13242340, rs2278293, rs2288549) and rejection and postoperative infection in renal transplant recipients were analyzed by SPSS 21 software. The result showed that IMPDH1 rs2288549 GG is a risk factor for acute rejection after renal transplantation (P<0.05), and IMPDH1 rs2278293 CT is a risk factor for infection after renal transplantation (P<0.05). Above all, IMPDH1 rs2288549 is an important factor of acute rejection after renal transplantation, IMPDH1 rs2278293 is an important factor affecting the emergence of infection after renal transplantation. The SNPs may help to optimize clinical medication to reduce the incidence of adverse reaction.

     

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