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 (CYP1A2) rs2470890 (RR = 2.857, 95% confidence interval = [1.392-5.863]), A allele of dopamine D2 (DRD2) rs1076560 (RR = 4.375, 95% confidence interval = [1.148-16.676]), T allele of paraoxonase-1 (PON1) 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 (CYP1A2, DRD2, and PON1) were associated with risk of tacrolimus-induced nephrotoxicity.
Keywords: Pharmacogenomics; liver transplantation; pediatric; renal toxicity; tacrolimus.