PXR基因多态性与心脏移植术后稳定期环孢素血药浓度的相关性  

Relationship between genetic polymorphisms of PXR and cyclosporine blood concentration of stable heart transplant recipients

作　　者：石秀锦[1] 魏国义[1] 林阳[1] 钟逾 张海波[3] 孟旭[3] 秦英[1] 李骁[1] 白玉国[1] 郑青敏[1] 周洋[1] 贾一新[3] 

机构地区：[1]首都医科大学附属北京安贞医院药剂科,北京100029 [2]毅新兴业(北京)科技有限公司,北京100080 [3]首都医科大学附属北京安贞医院心外科,北京100029

出　　处：《中国药物应用与监测》2014年第3期152-155,共4页Chinese Journal of Drug Application and Monitoring

摘　　要：目的:探讨心脏移植患者术后口服免疫抑制剂环孢素的血药浓度与PXR基因多态性的相关性。方法:应用飞行时间质谱技术对59例心脏移植术后稳定期患者的PXR基因型进行检测,全自动化学免疫分析仪测定环孢素的血药浓度,并通过统计学分析PXR各单核苷酸多态性(SNP)位点基因型对环孢素血药浓度的影响。结果:PXR基因筛选出的8个Tag SNP位点次要等位基因频率(MAF)与NCBI的dbSNP数据库中中国人的数据相近。对于59名稳定期心脏移植患者PXR基因8个Tag SNP中,仅携带PXR rs1523127(C 24381 A)位点AA型基因的患者血药浓度及校正血药浓度明显低于CA型,CA型又低于CC型患者,差异均具有统计学意义(P<0.05)。其他7个Tag SNP rs3814056T>G、rs7643645A>G、rs11917714C>T、rs2276705C>A、rs2472681T>C、rs2472682C>A、rs4440154C>T各基因型组间环孢素血药浓度的差异均无统计学意义。结论:PXR rs1523127(C 24381 A)基因型与心脏移植稳定期患者环孢素血药浓度显著相关,提示该SNP可能会在环孢素个体化用药中发挥重要作用。Objective： To investigate the correlation between gene polymorphisms of pregnane X receptor （PXR） and cyclosporine blood concentration in heart transplant patients. Methods：MassARRAY was applied to detect the PXR genotypes of 59 stable heart transplant recipients. AxSYM fully-automated chemistry immune analyzer was used to detect the blood concentration of cyclosporine. And then the inlfuence of the genotypes of PXR single nucleotide polymorphism （SNP） on cyclosporine trough blood concentration was analyzed by statistical method. Results：The minor allele frequency （MAF） in 8 tags of PXR SNP of 59 patients obtained in this study was similar with that in NCBI＆#39;s dbSNP database of Chinese population. The blood concentration and corrected concentration of cyclosporine in PXR rs1523127 （C 24381 A） AA patients were obviously lower than those of CA patients, and those of CA patients were obviously lower than those of CC patients （P〈 0.05）. There was no statistical difference in the cyclosporine blood concentrations in patients with the other seven PXR Tag SNP （rs3814056T〉G, rs7643645A〉G, rs11917714C〉T, rs2276705C〉A, rs2472681T〉C, rs2472682C〉A, rs4440154C〉T）. Conclusion：There was signiifcant correlation between PXR rs1523127 （C24381A） genotype and cyclosporine blood concentration in stable heart transplant recipients, which indicated that this SNP may play an important role in the individual application of cyclosporine.

关 键 词：飞行时间质谱技术 心脏移植 环孢素 血药浓度 孕烷X受体 基因多态性 

分 类 号：R969[医药卫生—药理学]