Association of CYP3A5 rs15524 and CYP3A7 rs776744 polymorphisms on tac IPV and clinical outcomes in early post-heart transplantation.

Background: The intrapatient variability (IPV) of tacrolimus (Tac) has gradually become a new index for the prognosis of organ transplantation. The gene polymorphism is involved in the pharmacokinetic process of Tac. The aim of this study was to investigate the effects of genetic polymorphisms on Tac IPV and other clinical outcomes in heart transplant recipients during the early post-transplantation period.

Methods: Our study retrospectively collected the clinical data and genotyping results of 48 heart transplant recipients. SPSS (21.0) and Graphpad Prism (8.0) were used to analyze the effect of gene polymorphism on Tac concentration (C₀) and clinical outcome.

Results: The CYP3A5 rs15524 AA genotype has a higher trough concentrations/dose (C₀/D) value than G allele carriers, and CYP3A7 rs776744 CC genotype has a higher C₀/D value than T allele carriers. Patients with The CYP3A5 rs15524 and CYP3A7 rs776744 mutants had a higher IPV. One year after heart transplantation, the mortality of wild-type and mutant CYP3A5 rs15524 patients due to rejection was 0 vs. 10.7% (P = 0.255). The mortality caused by rejection in wild-type patients and mutant patients of CYP3A7 rs776744 was 4.5% vs. 7.7% (p = 0.564).

Conclusions: Genetic polymorphisms of CYP3A5 rs15524 and CYP3A7 rs776744 affect tacrolimus metabolism in heart transplant recipients, significantly affecting Tac C₀/D during the early postoperative period. In addition, gene polymorphism may be related to Tac IPV and clinical outcome in patients with early heart transplantation.