Association Of CYP3A5 And C5 Polymorphisms With The Individual Dosage Regimen Of Tacrolimns In Chinese Liver Transplantation Recipients During The Early Post-transplantation Period

Purposes and contents Complement has been implicated in liver repair after toxic injury,liver cirrhosis and hepatic ischemia and reperfusion.Complement 5(C5)is a pivotal complement,which initiates the assembly of the membrane attack complex,and mediates liver regeneration and cirrhosis.we performed statistical analysis method to explore the association between C5 gene polymorphisms and HCC susceptibility or tacrolimus metabolism in the early stage after liver transplantation.Methods 145 adult patients who underwent primary LT for HCC were enrolled.Three single-nucleotide polymorphisms(SNPs)in C5 were genotyped and analyzed in case and control groups.The tacrolimus levels were monitored daily during the first week after transplantation.Results Patients with hepatocellular carcinoma or the C5 rs17611 allele G presented significantly higher tacrolimus C/D ratios in 2-4 two days after liver transplantation,Both donor and recipient CYP3A5 rs776746 polymorphisms were highly correlated with the tacrolimus C/D ratios at first week after liver transplantation.Recipient CYP3A5 rs776746 allele A,C5 rs17611 genotype AA,and donor CYP3A5 rs776746 allele A were associated with rapid tacrolimus metabolism.With increasing numbers of these alleles,patients were found to have lower tacrolimus C/D ratios during the one week after transplantation.Compared with the control group,the patients who harboring rs17611 allele G,rs25681 allele C and rs2300929 allele C can obviously increase the risk of HCC in the case group;haplotype rs17611Grs25681C-rs2300929 C notablely increased the risk of Hepatocellular Carcinoma(HCC)incidence,otherwise,haplotype rs17611A-rs25681T-rs2300929 T persisted as a beneficial factor for reducing the susceptibility of HCC.Conclusions recipient C5 rs17611 polymorphism is a new genetic locus that influences tacrolimus metabolism in patients after OLT during the early post-transplantation period.C5 gene polymorphisms are associated with the susceptibility of HCC.