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

Fecha de publicación: 03/02/2022 Fecha Ahead of Print: 03/02/2022

Autores de IIS La Fe

Luis Sendra Gisbert

Autor
Gladys Guadalupe Olivera Pasquini

Autor
Rafael López Andújar

Autor
Cristina Serrano Millan

Autor
Eva María Montalvá Orón

Autor
María José Herrero Cervera

Autor
Salvador F Aliño Pellicer

Autor

Participantes ajenos a IIS La Fe

Rojas LE

Grupos

Farmacogenética

Investigador Principal

María José Herrero Cervera
Hepatología, Cirugia Hepatobiliopancreática y Trasplantes

Leader

Marina Berenguer Haym

Abstract

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.

Datos de la publicación

ISSN/ISSNe:: 1999-4923, 1999-4923
Tipo:: Article
Páginas:: -
DOI:: 10.3390/pharmaceutics14020354
Factor de Impacto:: 0,922 SCImago ℠
Cuartil:: Q1 SCImago ℠

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Filiaciones

Sendra L:: Instituto de Investigación. Pharmacogenetics and Gene Therapy Unit, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain

Gene Therapy and Pharmacogenomics Group, Pharmacology Department, Faculty of Medicine, Universitat de València, Av. Blasco Ibáñez 15, Lab. 03, 46010 Valencia, Spain
Olivera GG:: Instituto de Investigación. Pharmacogenetics and Gene Therapy Unit, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain

Gene Therapy and Pharmacogenomics Group, Pharmacology Department, Faculty of Medicine, Universitat de València, Av. Blasco Ibáñez 15, Lab. 03, 46010 Valencia, Spain
López-Andújar R:: Unit of Hepatobiliopancreatic Surgery and Transplant, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain
Serrano C:: Instituto de Investigación. Spanish Clinical Research Network, SCReN, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain
Rojas LE:: Department of Internal Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 3542000, Chile

Program of Pharmacology and Toxicology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 3543151, Chile
Montalvá EM:: Unit of Hepatobiliopancreatic Surgery and Transplant, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain
Herrero MJ:: Instituto de Investigación. Pharmacogenetics and Gene Therapy Unit, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain

Gene Therapy and Pharmacogenomics Group, Pharmacology Department, Faculty of Medicine, Universitat de València, Av. Blasco Ibáñez 15, Lab. 03, 46010 Valencia, Spain
Aliño SF:: Instituto de Investigación. Pharmacogenetics and Gene Therapy Unit, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain

Gene Therapy and Pharmacogenomics Group, Pharmacology Department, Faculty of Medicine, Universitat de València, Av. Blasco Ibáñez 15, Lab. 03, 46010 Valencia, Spain

Unit of Clinical Pharmacology, Drugs Area, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain