MDR1 C1236T和G2677T/A基因多态性对肾移植受者他克莫司血药浓度影响的Meta分析
Chinese Journal of Hospital Pharmacy(2021)
Abstract
目的:系统评价多药耐药基因1 (MDR1)C1236T和G2677T/A多态性对肾移植受者他克莫司(FK506)血药浓度的影响,为临床个体化应用FK506提供循证参考.方法:计算机检索PubMed、Embase、Cochrane Library、CNKI数据库和万方数据库,检索时限均为建库起至2020年11月.收集MDR1 (C1236T,G2677T/A)基因多态性对肾移植受者FK506血药浓度影响的研究,用Rev Man 5.3软件进行Meta分析.结果:共纳入12篇(中文5篇,英文7篇)相关研究,共计1083例患者.其中,涉及C1236T的研究为9项,涉及G2677T/A的研究为10项.Meta分析结果显示:MDR1 C1236T基因型方面:MDR1 C1236T基因中CC型患者与CT型比较,FK506血药浓度/校正剂量值差异无统计学意义[SMD=2.18,95%CI(-2.84,7.19),P=0.40];MDR1 C1236T基因中CC型患者与TT型比较,FK506血药浓度/校正剂量值差异无统计学意义[SMD=6.02,95%CI(-4.12,16.17),P=0.24];MDR1 C1236T基因中CT型患者与TT型比较,FK506血药浓度/校正剂量值差异无统计学意义[SMD=-0.13,95%CI(-7.71,7.44),P=0.97].MDR1 G2677T/A基因型方面:MDR1 G2677T/A基因中GG型患者FK506血药浓度/校正剂量值显著低于GA+ GT型[SMD=-6.91,95%CI(-12.39,-1.42),P=0.01],亚组分析结果显示:术后12月[SMD=-18.62,95%CI(-23.41,-13.82),P<0.00001],MDR1 G2677T/A基因中GG型患者FK506血药浓度/校正剂量值显著低于GA+ GT型;MDR1 G2677T/A基因中GG型患者FK506血药浓度/校正剂量值显著低于TT+TA+ AA[SMD=-9.15,95%CI(-16.68,-1.61),P=0.02],亚组分析结果显示:术后12月[SMD=-19.81,95%CI(-39.29,-0.32),P=0.05],MDR1 G2677T/A基因中GG型患者FK506血药浓度/校正剂量值显著低于TT+ TA+ AA;MDR1 G2677T/A基因中GA+ GT型患者FK506血药浓度/校正剂量值与TT+ TA+ AA型比较,差异无统计学意义[SMD=-4.56,95%CI(-9.32,0.19),P=0.06].结论:MDR1G2677T/A基因多态性与FK506血药浓度/校正剂量值有一定的相关性,且GA+ GT或者TT+TA+ AA型>GG型,而MDR1 C1236T基因多态性与肾移植受者FK506血药浓度/校正剂量值无相关性.
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