MDR1 C3435T基因多态性与肾移植患者他克莫司血药浓度关系的Meta分析

目的:系统评价多药耐药基因1(MDR1)C3435T基因多态性与肾移植患者他克莫司(FK506)血药浓度的关系,为器官移植术后免疫抑制剂的精准化治疗提供循证参考。方法:计算机检索数据库Embase、Science Direct、Pubmed、CNKI、Wan fang、Conchrane,Clinicaltrials.gov,检索年限为1990年1月至2016年10月,检索语种为中文和英文,收集有关MDR1C3435T基因多态性与肾移植患者FK506血药浓度关系的研究。对纳入的研究进行资料提取与质量评价。用Cochrane提供Revman 5.3软件进行Meta分析。结果:有8项研究纳入此次Meta分析,共827例患者。Meta分析结果显示,MDR1C3435T基因型中CT型患者在肾移植术后1周MD=-16.93,95%CI(-27.67,-6.19),P=0.002]、1月MD=-18.09,95%CI(-26.41,-9.78),P<0.0001]、6月MD=-15.52,95%CI(-25.18,-5.85),P=0.002]时,血药浓度高于同期CC型患者;TT型患者在肾移植术后1周MD=-30.76,95%CI(-53.04,-8.48),P=0.007]、1月MD=-25.92,95%CI(-48.34,-3.51),P=0.02]、3月MD=-33.77,95%CI(-48.74,-18.80),P <0.00001]、6月MD=-22.25,95%CI(-32.97,-11.53),P<0.0001]、12月MD=-22.74,95%CI(-42.76,-2.72),P=0.03]时,血药浓度高于同期CC型患者;TT型患者在肾移植术后3月MD=-18.81,95%CI(-34.30,-3.33),P=0.002]时,血药浓度高于同期CT型患者。结论:MDR1C3435T基因多态性与FK506血药浓度/剂量存在相关性,且血药浓度的关系是携带者(CT型或者TT型)>非携带者(CC型)。在肾移植术后不同时期内,根据MDR1C3435T基因多态性与FK506血药浓度/剂量存在的相关性,做基因检测可以在短时间内达到有效血药浓度。由于纳入研究数量较少、样本量不大、该结论有待大样本、高质量研究进一步证实。

A Meta-analysis of correlation between MDR1 C3435T genotypes and blood concentration of tacrolimus in renal transplant recipients

OBJECTIVE To review the correlation between multi-drug resistance gene1 (MDR1) C3435T gene polymorphism and blood concentration of tacrolimus (FK506) in renal transplant recipients systematically, and to provide the evidence-based reference for the precise treatment of immunosuppressive agents after organ transplantation. METHODS Computer retrieval was applied to the following database from January 1990 to October 2016 in English and Chinese:Embase, Science Direct, Pubmed, CNKI, Wan fang, Conchrane, Clinicaltrials.gov. The studies about the correlation between MDR1 C3435T gene polymorphism and blood concentration of FK506 in renal transplant recipients were collected and evaluated in quality after extracting data. Then, Meta-analysis was performed using Revman 5.3 software. RESULTS Eight literatures with a total of 827 patients were involved in this meta-analysis. The results of Meta-analysis showed that 1 week (MD=-16.93, 95% CI (-27.67,-6.19), P=0.002), 1 month (MD=-18.09, 95% CI(-26.41,-9.78), P<0.0001) and 6 months (MD=-15.52, 95% CI (-25.18, -5.85), P=0.002) after renal transplant, the blood concentration/dose of FK506 was higher in patients with MDR1 C3435T type CT genotype than in CC genotype; 1 week (MD=-30.76, 95% CI (-53.04, -8.48), P=0.007), 1 month (MD=-25.92, 95% CI (-48.34,-3.51), P=0.02), 3 months (MD=-33.77, 95% CI (-48.74,-18.80), P<0.00001), 6 months (MD=-22.25, 95% CI (-32.97,-11.53), P<0.0001) and 12 months (MD=-22.74, 95% CI (-42.76,-2.72), P=0.03) after renal transplant, higher in patients with TT genotype than CC genotype; 3 months (MD=-18.81, 95% CI (-34.30,-3.33), P=0.002) after renal transplantation, higher in patients with TT genotype than in CT genotype. CONCLUSION MDR1 C3435T gene polymorphism is associated with FK506 plasma concentration/dose. And the relationship between plasma concentration is carrier (TT or CT type) >non-carrier (CC type). One year after renal transplantation, there is a correlation between MDR1 C3435T gene polymorphism and FK506 plasma concentration/dose, and gene testing can achieve effective plasma concentration in a shorter period. Due to the small number of included studies and not-large-enough samples, the conclusion needs to be further confirmed with large samples and high-quality research.