A new donors’ CYP3A5 and recipients’ CYP3A4 cluster predicting tacrolimus disposition, and new-onset hypertension in Chinese liver transplant patients

Abstract

Aim: The purpose of the current study was to investigate individualized therapy of tacrolimus (Tac), as well as complications after liver transplantation (LT) with the known genetic determinants and clinical factors.

Methods: In this retrospective study, two cohorts (n=170) from the China Liver Transplant Registry (CLTR) database from July 2007 to March 2015 were included.

Results: Both donors’ CYP3A5*3 and recipients’ CYP3A4*1G had a correlation with Tac pharmacokinetics at four weeks (all P<0.05), except recipients’ CYP3A4*1G nearly had an association at week 2 (P=0.055). The model of donors’ CYP3A5*3, recipients’ CYP3A4*1G, and total bilirubin (TBL), for the prediction of Tac disposition, was better than donors’ CYP3A5*3 only at week 1, 2, and 3 (P=0.010, P=0.007, and P=0.010, respectively), but not apparent at week 4 (P=0.297). Besides, when the P value was greater than or equal to 0.6685 after considering the false-positive rate R=10%, the patients were considered to have a faster metabolism, according to the mentioned model. Interestingly, we found that if more than or equal to two alleles A were present in the combination of donors’ CYP3A5*3 and recipients’ CYP3A4*1G genotype, there was a lower Tac C/D ration at week 1, 2, and 3 (P<0.001, P=0.001, and P<0.001), except at week 4 (P=0.082), and the probability of new-onset hypertension was lesser (P<0.001).

Conclusions: These data provided a potential basis for a comprehensive approach to predicting the Tac dose requirement in individual patients and provided a strategy for the effective prevention, early diagnosis of new-onset hypertension in Chinese LT recipients.