Combined effect of donor cytochrome P450 3A family polypeptide 5 and recipient cytochrome P450 3A family polypeptide 4 polymorphisms on the individual dosage regimen of tacrolimus in Chinese liver transplant patients

Abstract

Objective To investigate the effect of donor cytochrome P450 3A family polypeptide 5 (CYP3A5) and recipient cytochrome P450 3A family polypeptide 4 (CYP3A4) gene polymorphisms on the concentration/dose (C/D) ratio of tacrolimus in Chinese liver transplant patients.Methods Ninety liver transplant recipients treated with tacrolimus and their co-respective donors were enrolled in this study.Tacrolimus dosage and trough blood concentration were determined at 1 st month after liver transplantation.Polymerase chain reaction (PCR) amplification and DNA sequencing were applied to detect CYP3A5 rs776746 and CYP3A4 rs12333983 polymorphisms for all subjects.The relationship between gene polymorphisms and tacrolimus C/D ratios was analyzed.Results Both donor CYP3A5 rs776746 and recipient CYP3A4 rs12333983 polymorphisms were highly correlated with the tacrolimus C/D ratios at first month after liver transplantation.No linkage disequilibrium between donor CYP3A5 rs776746 and recipient CYP3A4 rs12333983 polymorphisms was observed (D' =0.017,r2 ＜ 0.001).The combined effect of these two polymorphisms demonstrated that there was significant difference in tacrolimus C/D ratio among groups.The trend of tacrolimus C/D ratios was highly significant at all investigated time points:extensive metabolizers (n =22) ＜ intermediate metabolizers (n =44) ＜ poor metabolizers (n =24).Conclusion Combined detection of donor CYP3A5 and recipient CYP3A4 genotypes may be performed prospectively to help individualize tacrolimus dose regimen for liver transplant patients. Key words: Liver transplantation; Tacrolimus ; Cytochrome P450 ; Gene polymorphism