摘要
目的 系统评价CYP3A5基因型与肾移植术后他克莫司（FK506）血药浓度的关系。方法 计算机检索PubMed（1966.1～2013.7）、Sciverse（1823.1～2013.7）、The Cochrane Library（2013年第7期）、CNKI（1994.1～2013.7）、VIP（1989.1-2013.7）、CBM（1978.1～2013.7）及WanFang Data（1995.1～2013.7），查找关于CYP3A5基因型与肾移植术后他克莫司（FK506）血药浓度/剂量关系的文献。根据纳入与排除标准筛选文献、提取资料和评价质量后，采用RevMan 5.2软件进行Meta分析。结果 共纳入12篇文献，包含956例对象。Meta分析结果显示：在肾移植术后7天［MD=54.61，95%CI（–67.67，–41.54），P〈0.000 01］、1个月［MD= –74.84，95%CI（–83.39，–66.29），P〈0.000 01］、3个月［MD= –96.09，95%CI（–107.55，–84.64），P〈0.000 01］、6个月［MD= –107.30，95%CI（–125.65，–88.95），P〈0.000 01］和1年［MD= –78.32，95%CI（–123.02，–33.61），P=0.000 6］，携带CYP3A5 ＊3/＊3基因型患者的FK506 血药浓度/剂量值明显较携带其他基因型患者高；而携带＊1/＊1患者的FK506 血药浓度/剂量值较低。结论 肾移植术后FK506血药浓度/剂量值与CYP3A5基因型相关。因此在肾移植术后应用FK506作为免疫抑制治疗时，有必要对患者进行CYP3A5基因型检测，以指导临床治疗。
Objective To systematically review the correlation between CYP3A5 genotypes and blood levels of tacrolimus （FK506） in renal transplant recipients. Methods Such databases as PubMed （January 1966 to July 2013）, Sciverse （January 1823 to July 2013）, The Cochrane Library （Issue 7, 2013）, CNKI （January 1994 to July 2013）, VIP （January 1989 to July 2013）, CBM （January 1978 to July 2013） and WanFang Data （January 1995 to July 2013） were electronically searched for studies about the correlation between CYP3A5 genotypes and FK506 （blood concentration/dose-respones relationship） in renal transplant recipients. According to the inclusion and exclusion criteria, literature was screened, data were extracted, and the methodological quality of included studies was also assessed. Then, meta-analysis was performed using RevMan 5.2 software. Results A total of 12 articles involving 956 patients were included. The results of meta-analysis showed that, after renal transplantation, there was a high dose-adjusted concentration of CYP3A5 ＊3/＊3 carriers on the 7th day （MD= 54.61, 95%CI –67.67 to –41.54, P〈0.000 01）, in the 1st month （MD= –74.84, 95%CI –83.39 to –66.29, P〈0.000 01）, in the 3rd month （MD= –96.09, 95%CI –107.55 to –84.64, P〈0.000 01）, in the 6th month （MD= –107.30, 95%CI –125.65 to –88.95, P〈0.000 01）, and in the 1st year （MD= –78.32, 95%CI –123.02 to –33.61, P=0.000 6）. The dose-adjusted concentration of FK506 in CYP3A5 ＊3/＊3 patients was higher than the other genotypes, while the dose-adjusted concentration of FK506 in CYP3A5 ＊1/＊1 patients was low. Conclusion The blood concentration as well as dose-respones relationship of FK506 are associated with CYP3A5 genotype in renal transplant recipients. We propose that patients with renal transplantation should receive CYP3A5 genotypes test to determine the use of FK506 as an immunosuppressant, so as to guide its clinical application.
出处
《中国循证医学杂志》
CSCD
2013年第12期1440-1445,共6页
Chinese Journal of Evidence-based Medicine
基金
甘肃省科技支撑计划项目(编号:1011FKCA090)
兰州大学第二医院院内课题(编号:v200805)
