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

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dc.contributor.authorSendra, Luis
dc.contributor.authorOlivera, Gladys G.
dc.contributor.authorLopez-Andujar, Rafael
dc.contributor.authorSerrano, Cristina
dc.contributor.authorRojas, Luis E.
dc.contributor.authorMaria Montalva, Eva
dc.contributor.authorJose Herrero, Maria
dc.contributor.authorAlino, Salvador F.
dc.date.accessioned2025-01-20T21:09:49Z
dc.date.available2025-01-20T21:09:49Z
dc.date.issued2022
dc.description.abstractSome 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.
dc.fuente.origenWOS
dc.identifier.doi10.3390/pharmaceutics14020354
dc.identifier.eissn1999-4923
dc.identifier.urihttps://doi.org/10.3390/pharmaceutics14020354
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/93547
dc.identifier.wosidWOS:000774806300001
dc.issue.numero2
dc.language.isoen
dc.revistaPharmaceutics
dc.rightsacceso restringido
dc.subjectpharmacogenetics
dc.subjectimmunosuppressant
dc.subjectABC
dc.subjectCYP
dc.subjectSLCO
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titlePharmacogene Variants Associated with Liver Transplant in a Twelve-Year Clinical Follow-Up
dc.typeartículo
dc.volumen14
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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