CYP3A5 and POR gene polymorphisms as predictors of infection and graft rejection in post-liver transplant patients treated with tacrolimus

CYP3A5 and POR gene polymorphisms as predictors of infection and graft rejection in post-liver transplant patients treated with tacrolimus - a cohort study

Published:2023-10-09 Issue: Volume: Page:
ISSN:
Container-title:
language:
Short-container-title:

Author:

Ono Suzane¹,Naldi Graziella²,Minari Ariane²,Pereira Thales,Fossaluza Victor,Eugenio Nicholas,Ferreira Marcelo,Gregório Guilherme^ORCID,Nacif Lucas,Albuquerque Luiz D,Filho Ricardo di Lazzaro,Cançado Eduardo,Ono Suzane¹

Affiliation:

1. University of São Paulo School of Medicine

2. Universidade de São Paulo

Abstract

Abstract Liver transplantation is the only curative option for patients with advanced stages of liver disease, with tacrolimus used as the immunosuppressive drug of choice. However, due to its narrow therapeutic index and high inter- and intra-individual variability, serum monitoring should be frequent. An individual's genetic variability can interfere with drug response, potentially leading an individual to overexposure or underexposure of a drug. This study aims to investigate the association of polymorphisms with infection, acute rejection, and renal failure. This is an observational, prospective, cohort, single-center study in liver transplant patients. Were collected 97 recipients and 97 donors. The logistic regression model found an influence of patients expressing CYP3A5*3 (rs776746) and expressing POR*28 (rs1057868) on the development of acute rejection after liver transplantation (p = 0.028). It also found an association between carriers of the variant allele of the POR*28 gene and infection (p = 0.006 isolated analysis and p = 0.003 combined analysis).

Publisher

Research Square Platform LLC

Reference30 articles.

1. Centers for Disease Control and Prevention. Chronic Liver Disease Cirrhosis. 2020 [cited 2022 Aug 26]. Chronic Liver Disease Cirrhosis. Available from: https://www.cdc.gov/nchs/fastats/liver-disease.htm

2. Adam R, Karam V, Cailliez V, O Grady JG, Mirza D, Cherqui D, et al. 2018 Annual Report of the European Liver Transplant Registry (ELTR) – 50-year evolution of liver transplantation. Transplant International. 2018;31(12).

3. Liver transplantation;EASL Clinical Practice Guidelines;J Hepatol,2016

4. High Intrapatient Variability of Tacrolimus Exposure in the Early Period After Liver Transplantation Is Associated With Poorer Outcomes;Rayar M;Transplantation,2018

5. Brunet M, Pastor-Anglada M. Insights into the Pharmacogenetics of Tacrolimus Pharmacokinetics and Pharmacodynamics. Vol. 14, Pharmaceutics. MDPI; 2022.