Impact of genetic polymorphisms on tacrolimus concentrations and intra-individual variability in recipients of heart transplants during the early post-heart transplantation period

TL;DR

This study investigates how genetic differences influence tacrolimus blood levels and variability in early post-heart transplant patients, highlighting the importance of genotyping for personalized medication management.

Contribution

It identifies specific genetic polymorphisms associated with tacrolimus variability, providing new insights for optimizing post-transplant immunosuppressive therapy.

Findings

CYP3A5*1D and CYP3A7 rs776744 haplotypes significantly affect intra-individual variability.

Low body weight and high neutrophil percentage influence tacrolimus variability.

Genotyping can help tailor dosing to improve outcomes.

Abstract

This study aimed to investigate the effects of genetic polymorphisms on tacrolimus blood levels and intra-individual variability in recipients of heart transplants during the early post-transplantation period. Demographic information, concomitant medications, daily tacrolimus dose, trough concentration, and physiological and biochemical information of 87 Chinese recipients of heart transplants were collected. Trough concentrations were determined using a chemiluminescent micro-particle immunoassay, and 17 selected single nucleic acid polymorphisms were genotyped by direct sequencing. We assessed intra-individual variability by calculating the coefficient of variation of tacrolimus trough concentration and analyzed factors associated with tacrolimus concentration and intra-individual variability. Our study found that low body weight and a high percentage of neutrophils significantly influenced the coefficient of variation of tacrolimus. CYP3A5*1D and CYP3A7 rs776744 haplotypes correlated significantly with an intra-individual coefficient of variation of tacrolimus trough concentration during the early postoperative period. Patients with the CYP3A5*1D rs15524 and CYP3A7 rs776744 TT haplotype had a higher coefficient of variation than carriers of the C allele. Genetic polymorphisms in recipients of heart transplants affect tacrolimus metabolism, significantly affecting tacrolimus blood concentration during the early postoperative period. Genotyping before drug administration can help optimize dosing regimens, reduce intra-individual variability, and improve prognosis.