Pharmacogenetics association with long-term clinical evolution in a kidney transplant patients cohort
Background: Pharmacogenetic variability has been reported to influence the efficacy and safety of immunosuppressive therapies in early stages of kidney transplantation. This study investigates long-term associations between pharmacogene variants and clinical outcomes in a cohort of kidney transplant...
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Elsevier
2025-01-01
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| Series: | Current Research in Pharmacology and Drug Discovery |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590257125000185 |
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| author | Luis Sendra Gladys G. Olivera-Pasquini Enrique G. Zucchet Fabiana D.V. Genvigir María Isabel Beneyto Julio Hernández-Jaras María José Herrero Salvador F. Aliño |
| author_facet | Luis Sendra Gladys G. Olivera-Pasquini Enrique G. Zucchet Fabiana D.V. Genvigir María Isabel Beneyto Julio Hernández-Jaras María José Herrero Salvador F. Aliño |
| author_sort | Luis Sendra |
| collection | DOAJ |
| description | Background: Pharmacogenetic variability has been reported to influence the efficacy and safety of immunosuppressive therapies in early stages of kidney transplantation. This study investigates long-term associations between pharmacogene variants and clinical outcomes in a cohort of kidney transplant recipients over a 12-year follow-up. Materials and methods: We analyzed 37 SNPs from 14 genes related to drug metabolism and transport in 79 kidney transplant patients. Clinical parameters, including survival, renal function, tumor occurrence, and pharmacokinetics of tacrolimus, were evaluated. Logistic regression and Kaplan-Meier analyses assessed associations between gene variants and clinical outcomes. Results: Variants in metabolizer (CYP3A5, CYP2B6) and transporter genes (ABCB1, ABCC2) were associated with 12-year survival. Increased tumor risk correlated with ABCC2 variants in donors and decreased risk with CYP2B6 rs3745274 in recipients. Renal function was influenced by variants in ABCB1, ABCC2, CYP3A5, CYP3A4, and CYP2B6. Tacrolimus dose-dependent concentration was affected by variants in CYP3A4, CYP3A5, CYP2C19, ABCB1, and SLCO1B1. Increased nephrotoxicity risk was associated with CYP2C19 rs4244285 and reduced by SLCO1B1 rs2306283 AA and AG variants. Gene variant interactions between metabolizer and transporter genes were also associated with altered risk of events incidence. Discussion: Our findings support that pharmacogene variants influence transplant outcomes. Notable associations include survival related to ABCB1 and ABCC2 variants, tumor occurrence linked to CYP2B6 rs3745274, and renal function affected by multiple pharmacogenes. Variants in CYP2C19 and SLCO1B1 significantly impacted tacrolimus pharmacokinetics and nephrotoxicity risk. These results underline the importance of pharmacogenetic testing for personalized management in kidney transplantation, although further validation in larger cohorts is necessary. |
| format | Article |
| id | doaj-art-a3098baaea0e49ab90cd12f8d07024e4 |
| institution | DOAJ |
| issn | 2590-2571 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
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| series | Current Research in Pharmacology and Drug Discovery |
| spelling | doaj-art-a3098baaea0e49ab90cd12f8d07024e42025-08-20T02:45:27ZengElsevierCurrent Research in Pharmacology and Drug Discovery2590-25712025-01-01910023010.1016/j.crphar.2025.100230Pharmacogenetics association with long-term clinical evolution in a kidney transplant patients cohortLuis Sendra0Gladys G. Olivera-Pasquini1Enrique G. Zucchet2Fabiana D.V. Genvigir3María Isabel Beneyto4Julio Hernández-Jaras5María José Herrero6Salvador F. Aliño7Gene Therapy and Pharmacogenomics, Department of Pharmacology, University of Valencia, 46010, Valencia, Spain; Pharmacogenetics and Gene Therapy Unit, La Fe Health Research Institute, 46026, Valencia, SpainGene Therapy and Pharmacogenomics, Department of Pharmacology, University of Valencia, 46010, Valencia, Spain; Pharmacogenetics and Gene Therapy Unit, La Fe Health Research Institute, 46026, Valencia, SpainPharmacogenetics and Gene Therapy Unit, La Fe Health Research Institute, 46026, Valencia, SpainDepartment of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, 05508-000, Sao Paulo, BrazilUrology and Nephrology Service, University and Polytechnic La Fe Hospital, 46026, Valencia, SpainUrology and Nephrology Service, University and Polytechnic La Fe Hospital, 46026, Valencia, SpainGene Therapy and Pharmacogenomics, Department of Pharmacology, University of Valencia, 46010, Valencia, Spain; Pharmacogenetics and Gene Therapy Unit, La Fe Health Research Institute, 46026, Valencia, Spain; Corresponding author. Gene Therapy and Pharmacogenomics Group, Department of Pharmacology, Faculty of Medicine, Universitat de València, Av. Blasco Ibáñez 15, lab. 03, 46010, Valencia, Spain.Gene Therapy and Pharmacogenomics, Department of Pharmacology, University of Valencia, 46010, Valencia, SpainBackground: Pharmacogenetic variability has been reported to influence the efficacy and safety of immunosuppressive therapies in early stages of kidney transplantation. This study investigates long-term associations between pharmacogene variants and clinical outcomes in a cohort of kidney transplant recipients over a 12-year follow-up. Materials and methods: We analyzed 37 SNPs from 14 genes related to drug metabolism and transport in 79 kidney transplant patients. Clinical parameters, including survival, renal function, tumor occurrence, and pharmacokinetics of tacrolimus, were evaluated. Logistic regression and Kaplan-Meier analyses assessed associations between gene variants and clinical outcomes. Results: Variants in metabolizer (CYP3A5, CYP2B6) and transporter genes (ABCB1, ABCC2) were associated with 12-year survival. Increased tumor risk correlated with ABCC2 variants in donors and decreased risk with CYP2B6 rs3745274 in recipients. Renal function was influenced by variants in ABCB1, ABCC2, CYP3A5, CYP3A4, and CYP2B6. Tacrolimus dose-dependent concentration was affected by variants in CYP3A4, CYP3A5, CYP2C19, ABCB1, and SLCO1B1. Increased nephrotoxicity risk was associated with CYP2C19 rs4244285 and reduced by SLCO1B1 rs2306283 AA and AG variants. Gene variant interactions between metabolizer and transporter genes were also associated with altered risk of events incidence. Discussion: Our findings support that pharmacogene variants influence transplant outcomes. Notable associations include survival related to ABCB1 and ABCC2 variants, tumor occurrence linked to CYP2B6 rs3745274, and renal function affected by multiple pharmacogenes. Variants in CYP2C19 and SLCO1B1 significantly impacted tacrolimus pharmacokinetics and nephrotoxicity risk. These results underline the importance of pharmacogenetic testing for personalized management in kidney transplantation, although further validation in larger cohorts is necessary.http://www.sciencedirect.com/science/article/pii/S2590257125000185TransplantationImmunosuppressionPharmacogeneticsLong-term evolutionGene variantsClinical evolution |
| spellingShingle | Luis Sendra Gladys G. Olivera-Pasquini Enrique G. Zucchet Fabiana D.V. Genvigir María Isabel Beneyto Julio Hernández-Jaras María José Herrero Salvador F. Aliño Pharmacogenetics association with long-term clinical evolution in a kidney transplant patients cohort Current Research in Pharmacology and Drug Discovery Transplantation Immunosuppression Pharmacogenetics Long-term evolution Gene variants Clinical evolution |
| title | Pharmacogenetics association with long-term clinical evolution in a kidney transplant patients cohort |
| title_full | Pharmacogenetics association with long-term clinical evolution in a kidney transplant patients cohort |
| title_fullStr | Pharmacogenetics association with long-term clinical evolution in a kidney transplant patients cohort |
| title_full_unstemmed | Pharmacogenetics association with long-term clinical evolution in a kidney transplant patients cohort |
| title_short | Pharmacogenetics association with long-term clinical evolution in a kidney transplant patients cohort |
| title_sort | pharmacogenetics association with long term clinical evolution in a kidney transplant patients cohort |
| topic | Transplantation Immunosuppression Pharmacogenetics Long-term evolution Gene variants Clinical evolution |
| url | http://www.sciencedirect.com/science/article/pii/S2590257125000185 |
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