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Pharmacogene Variants Associated with Liver Transplant in a Twelve-Year Clinical Follow-Up

Some gene polymorphisms have been previously associated individually with tacrolimus efficacy and toxicity, but no long-term study to determine the role of pharmacogene variants in the clinical evolution of liver-transplanted patients has been addressed so far. In the present work, we analyzed the r...

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Autores principales: Sendra, Luis, Olivera, Gladys G., López-Andújar, Rafael, Serrano, Cristina, Rojas, Luis E., Montalvá, Eva María, Herrero, María José, Aliño, Salvador F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8878556/
https://www.ncbi.nlm.nih.gov/pubmed/35214086
http://dx.doi.org/10.3390/pharmaceutics14020354
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author Sendra, Luis
Olivera, Gladys G.
López-Andújar, Rafael
Serrano, Cristina
Rojas, Luis E.
Montalvá, Eva María
Herrero, María José
Aliño, Salvador F.
author_facet Sendra, Luis
Olivera, Gladys G.
López-Andújar, Rafael
Serrano, Cristina
Rojas, Luis E.
Montalvá, Eva María
Herrero, María José
Aliño, Salvador F.
author_sort Sendra, Luis
collection PubMed
description Some gene polymorphisms have been previously associated individually with tacrolimus efficacy and toxicity, but no long-term study to determine the role of pharmacogene variants in the clinical evolution of liver-transplanted patients has been addressed so far. In the present work, we analyzed the relation between highly-evidenced genetic polymorphisms located in relevant pharmacogenes and the risk of suffering premature death and other comorbidities such as cancer, diabetes mellitus, arterial hypertension, graft rejection, infections and nephrotoxicities in a cohort of 87 patients (8 were excluded due to early loss of follow-up) transplanted at Hospital La Fe in Valencia (Spain) during a 12-year follow-up. Employing a logistic regression model with false discovery rate penalization and Kaplan–Meier analyses, we observed significant association between survival rates and metabolizer genes. In this sense, our results show an association between MTHFR gene variants in donor rs1801133 (HR: 7.90; p-value: 0.032) and recipient rs1801131 (HR: 7.34; p-value: 0.036) and the group of patients who died during the follow-up period, supporting the interest of confirming these results with larger patient cohorts. In addition, donor polymorphisms in UGT1A9 metabolizer gene rs6714486 (OR: 0.13; p-value: 0.032) were associated with a lower risk of suffering from de novo cancer. Genetic variants in CYP2B6 metabolizer gene rs2279343 demonstrated an association with a risk of infection. Other variants in different locations of SLCO1A2, ABCC2 and ABCB1 transporter genes were associated with a lower risk of suffering from type 2 diabetes mellitus, chronic and acute nephrotoxicities and arterial hypertension. Results suggest that pharmacogenetics-derived information may be an important support for personalized drug prescription, clinical follow-up and the evolution of liver-transplanted patients.
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spelling pubmed-88785562022-02-26 Pharmacogene Variants Associated with Liver Transplant in a Twelve-Year Clinical Follow-Up Sendra, Luis Olivera, Gladys G. López-Andújar, Rafael Serrano, Cristina Rojas, Luis E. Montalvá, Eva María Herrero, María José Aliño, Salvador F. Pharmaceutics Article Some gene polymorphisms have been previously associated individually with tacrolimus efficacy and toxicity, but no long-term study to determine the role of pharmacogene variants in the clinical evolution of liver-transplanted patients has been addressed so far. In the present work, we analyzed the relation between highly-evidenced genetic polymorphisms located in relevant pharmacogenes and the risk of suffering premature death and other comorbidities such as cancer, diabetes mellitus, arterial hypertension, graft rejection, infections and nephrotoxicities in a cohort of 87 patients (8 were excluded due to early loss of follow-up) transplanted at Hospital La Fe in Valencia (Spain) during a 12-year follow-up. Employing a logistic regression model with false discovery rate penalization and Kaplan–Meier analyses, we observed significant association between survival rates and metabolizer genes. In this sense, our results show an association between MTHFR gene variants in donor rs1801133 (HR: 7.90; p-value: 0.032) and recipient rs1801131 (HR: 7.34; p-value: 0.036) and the group of patients who died during the follow-up period, supporting the interest of confirming these results with larger patient cohorts. In addition, donor polymorphisms in UGT1A9 metabolizer gene rs6714486 (OR: 0.13; p-value: 0.032) were associated with a lower risk of suffering from de novo cancer. Genetic variants in CYP2B6 metabolizer gene rs2279343 demonstrated an association with a risk of infection. Other variants in different locations of SLCO1A2, ABCC2 and ABCB1 transporter genes were associated with a lower risk of suffering from type 2 diabetes mellitus, chronic and acute nephrotoxicities and arterial hypertension. Results suggest that pharmacogenetics-derived information may be an important support for personalized drug prescription, clinical follow-up and the evolution of liver-transplanted patients. MDPI 2022-02-03 /pmc/articles/PMC8878556/ /pubmed/35214086 http://dx.doi.org/10.3390/pharmaceutics14020354 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sendra, Luis
Olivera, Gladys G.
López-Andújar, Rafael
Serrano, Cristina
Rojas, Luis E.
Montalvá, Eva María
Herrero, María José
Aliño, Salvador F.
Pharmacogene Variants Associated with Liver Transplant in a Twelve-Year Clinical Follow-Up
title Pharmacogene Variants Associated with Liver Transplant in a Twelve-Year Clinical Follow-Up
title_full Pharmacogene Variants Associated with Liver Transplant in a Twelve-Year Clinical Follow-Up
title_fullStr Pharmacogene Variants Associated with Liver Transplant in a Twelve-Year Clinical Follow-Up
title_full_unstemmed Pharmacogene Variants Associated with Liver Transplant in a Twelve-Year Clinical Follow-Up
title_short Pharmacogene Variants Associated with Liver Transplant in a Twelve-Year Clinical Follow-Up
title_sort pharmacogene variants associated with liver transplant in a twelve-year clinical follow-up
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8878556/
https://www.ncbi.nlm.nih.gov/pubmed/35214086
http://dx.doi.org/10.3390/pharmaceutics14020354
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