Association of CYP3A5 and C5 polymorphisms with the individual dosage regimen of tacrolimus in Chinese liver transplantation recipients during the early post-transplantation period / 中华器官移植杂志

ABSTRACT

Objective To investigate the effect of CYP3A5 and C5 gene polymorphisms on the concentration/dose ratio of tacrolimus in Chinese liver transplant patients during the early posttransplantation period.Methods A total of 100 adult patients who underwent primary liver transplantation (LT) were enrolled.Tacrolimus dosage and trough blood concentration were detemined at first week after liver transplantation.Two single-nucleotide polymorphisms were genotyped and analyzed in both donor and recipient groups.The relationship between gene polymorphisms and tacrolimus concentration/dose ratio (C/ D ratio) was analyzed.Results The distribution of allele A in C5 rs17611 was 63.5 ％ among donors and 58.5％ among recipients.For CYP3A5,the rs776746 allele G represented the major alleles in both donors and recipients (71％ and 72％,respectively).The tacrolimus C/D ratio of recipients carrying allele AA in C5 rs17611 was significantly higher than that of recipients carrying the C5 rs17611 allele G.Both donor and recipient CYP3A5 rs776746 polymorphisms were highly correlated with the tacrolimus C/D ratio at first week after liver transplantation.No linkage disequilibrium between CYP3A5 rs776746 and C5 rs17611 polymorphisms was found (D'max =0.392,r2max =0.034).Recipient CYP3A5 rs776746 allele A,C5 rs17611 genotype AA,and donor CYP3A5 rs776746 allele A were associated with rapid tacrolimus metabolism.With increasing number of these alldes,tacrolimus C/D ratio was reduced during the one week after transplantation.Conclusion Recipient C5 rs17611 polymorphism is a new genetic locus that influences tacrolimus metabolism in patients after OLT during the early post-transplantation periocd.