Wang Dongdong, Chen Xiao, Fu Meng, Xu Hong, Li Zhiping
Department of Pharmacy, Children's Hospital of Fudan University, Shanghai, China.
Department of Nephrology, Children's Hospital of Fudan University, Shanghai, China.
Xenobiotica. 2020 Apr;50(4):488-493. doi: 10.1080/00498254.2019.1652782. Epub 2019 Aug 14.
Survival for pediatric liver transplantation patients is limited by nephrotoxicity of calcineurin inhibitors tacrolimus. The present study was to explore the association of genetic factors with nephrotoxicity of pediatric liver transplantation patients treated with tacrolimus.Chinese pediatric liver transplantation patients under tacrolimus therapy between March 2014 and August 2018 from Children's Hospital of Fudan University were retrospectively analyzed. A total of 15 patients, including 6 patients with nephrotoxicity induced by tacrolimus and 9 patients without nephrotoxicity, were detected by pharmacogenomics (PGxOne®160). Demographic characteristics and laboratory testing were collected from medical logs. Tacrolimus blood concentrations were extracted from therapeutic drug monitoring (TDM) documents.The risk of renal toxicity induced by tacrolimus in Chinese pediatric liver transplantation patients were positively associated with T allele of cytochrome P450 1A2 () rs2470890 (RR = 2.857, 95% confidence interval = [1.392-5.863]), A allele of dopamine D2 () rs1076560 (RR = 4.375, 95% confidence interval = [1.148-16.676]), T allele of paraoxonase-1 () rs662 (RR = 2.800, 95% confidence interval= [1.184-6.622]), respectively.Pharmacogenomics analysis in Chinese pediatric liver transplantation patients with renal toxicity induced by tacrolimus was firstly reported. The SNPs in 3 genes (, , and ) were associated with risk of tacrolimus-induced nephrotoxicity.
儿童肝移植患者的生存受到钙调神经磷酸酶抑制剂他克莫司肾毒性的限制。本研究旨在探讨基因因素与接受他克莫司治疗的儿童肝移植患者肾毒性之间的关联。对2014年3月至2018年8月在复旦大学附属儿科医院接受他克莫司治疗的中国儿童肝移植患者进行回顾性分析。通过药物基因组学（PGxOne®160）检测了15例患者，其中包括6例他克莫司诱导的肾毒性患者和9例无肾毒性患者。从医疗记录中收集人口统计学特征和实验室检查结果。从治疗药物监测（TDM）文件中提取他克莫司血药浓度。中国儿童肝移植患者中他克莫司诱导的肾毒性风险分别与细胞色素P450 1A2（）rs2470890的T等位基因（RR = 2.857，95%置信区间= [1.392 - 5.863]）、多巴胺D2（）rs1076560的A等位基因（RR = 4.375，95%置信区间= [1.148 - 16.676]）、对氧磷酶-1（）rs662的T等位基因（RR = 2.800，95%置信区间= [1.184 - 6.622]）呈正相关。首次报道了对中国儿童肝移植患者他克莫司诱导的肾毒性进行的药物基因组学分析。3个基因（、和）中的单核苷酸多态性与他克莫司诱导的肾毒性风险相关。
