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

Effects of MDR1 C1236T and G2677T/A genetic polymorphism on blood concentration of tacrolimus in renal transplant recipients: a Meta-analysis

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1 083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<0.000 01],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。

OBJECTIVE To systematically assess the effects of MDR1 C1236 T and G2677 T/A genetic polymorphism on blood concentration of tacrolimus in renal transplant recipients.METHODS The databases of Cochrane Library, PubMed, Embase, CNKI and WanFang were searched from the inceptions to November 2020 and the related literature reports manually searched regarding the impact of MDR1(C1236 T,G2677 T/A)genetic polymorphism on blood concentration of tacrolimus.Meta-analysis was performed by Rev Man 5.3 software.RESULTS A total of 12 studies(5 papers in Chinese and 7 papers in English)were included, involving 1 083 adult renal transplant recipients.Among these, 9 and 10 studies involved C1236 T and G2677 T/A respectively.Meta-analysis revealed that in terms of MDR1 C1236 T genotype, no significant difference existed in blood concentration/adjusted dose of FK506 between MDR1 C1236 T CC and CT genotypes [SMD=2.18,95%CI(-2.84,7.19),P=0.40];no significant difference in blood concentration/adjusted dose of FK506 between MDR1 C1236 T CC and TT genotypes [SMD=6.02,95%CI(-4.12,16.17),P=0.24];no significant difference in blood concentration/adjusted dose of FK506 between MDR1 C1236 T CT and TT genotypes [SMD=-0.13,95%CI(-7.71,7.44),P=0.97].Also Meta-analysis indicated that in terms of G2677 T/A genotype, blood concentration/adjusted dose of FK506 in MDR1 G2677 T/A GG genotype was significantly lower than that in GA+GT genotype [SMD=-6.91,95%CI(-12.39,-1.42),P=0.01].Subgroup analysis showed that 12 months post-operation [SMD=-18.62,95%CI(-23.41,-13.82),P<0.000 01],blood concentration/adjusted dose of FK506 in MDR1 G2677 T/A GG genotype was significantly lower than that in GA+GT genotype;blood concentration/adjusted dose of FK506 in MDR1 G2677 T/A GG genotype was significantly lower than that in TT+TA+AA genotype [SMD=-9.15,95%CI(-16.68,-1.61),P=0.02].Subgroup analysis showed that 12 months post-operation [SMD=-19.81,95%CI(-39.29,-0.32),P=0.05],blood concentration/adjusted dose of FK506 in MDR1 G2677 T/A GG genotype was significantly lower than that in TT+TA+AA genotype;no significant difference existed in blood concentration/adjusted dose of FK506 between MDR1 G2677 T/A GA+GT genotype and TT+TA+AA type [SMD=-4.56,95%CI(-9.32,0.19),P=0.06].CONCLUSION MDR1 G2677 T/A gene polymorphisms are correlated with blood concentration/adjusted dose of FK506,GA+GT or TT+TA+AA genotype>GG genotype.However, MDR1 C1236 T gene polymorphisms are not correlated with blood concentration/adjusted dose of FK506 in renal transplant recipients.