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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MDPI AG
2022-02-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/2/354 |
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| author | Luis Sendra Gladys G. Olivera Rafael López-Andújar Cristina Serrano Luis E. Rojas Eva María Montalvá María José Herrero Salvador F. Aliño |
| author_facet | Luis Sendra Gladys G. Olivera Rafael López-Andújar Cristina Serrano Luis E. Rojas Eva María Montalvá María José Herrero Salvador F. Aliño |
| author_sort | Luis Sendra |
| collection | DOAJ |
| 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; <i>p</i>-value: 0.032) and recipient rs1801131 (HR: 7.34; <i>p</i>-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 <i>UGT1A9</i> metabolizer gene rs6714486 (OR: 0.13; <i>p</i>-value: 0.032) were associated with a lower risk of suffering from de novo cancer. Genetic variants in <i>CYP2B6</i> metabolizer gene rs2279343 demonstrated an association with a risk of infection. Other variants in different locations of <i>SLCO1A2</i>, <i>ABCC2</i> and <i>ABCB1</i> transporter genes were associated with a lower risk of suffering from type 2 <i>diabetes mellitus</i>, 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. |
| first_indexed | 2024-03-09T21:14:30Z |
| format | Article |
| id | doaj.art-ef4c0928c608413686ce06ae87694258 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T21:14:30Z |
| publishDate | 2022-02-01 |
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| spelling | doaj.art-ef4c0928c608413686ce06ae876942582023-11-23T21:37:54ZengMDPI AGPharmaceutics1999-49232022-02-0114235410.3390/pharmaceutics14020354Pharmacogene Variants Associated with Liver Transplant in a Twelve-Year Clinical Follow-UpLuis Sendra0Gladys G. Olivera1Rafael López-Andújar2Cristina Serrano3Luis E. Rojas4Eva María Montalvá5María José Herrero6Salvador F. Aliño7Pharmacogenetics and Gene Therapy Unit, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, SpainPharmacogenetics and Gene Therapy Unit, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, SpainUnit of Hepatobiliopancreatic Surgery and Transplant, Hospital Universitario y Politécnico La Fe, 46026 Valencia, SpainSpanish Clinical Research Network, SCReN, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, SpainDepartment of Internal Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 3542000, ChileUnit of Hepatobiliopancreatic Surgery and Transplant, Hospital Universitario y Politécnico La Fe, 46026 Valencia, SpainPharmacogenetics and Gene Therapy Unit, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, SpainPharmacogenetics and Gene Therapy Unit, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, SpainSome 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; <i>p</i>-value: 0.032) and recipient rs1801131 (HR: 7.34; <i>p</i>-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 <i>UGT1A9</i> metabolizer gene rs6714486 (OR: 0.13; <i>p</i>-value: 0.032) were associated with a lower risk of suffering from de novo cancer. Genetic variants in <i>CYP2B6</i> metabolizer gene rs2279343 demonstrated an association with a risk of infection. Other variants in different locations of <i>SLCO1A2</i>, <i>ABCC2</i> and <i>ABCB1</i> transporter genes were associated with a lower risk of suffering from type 2 <i>diabetes mellitus</i>, 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.https://www.mdpi.com/1999-4923/14/2/354pharmacogeneticsimmunosuppressantABCCYPSLCO |
| spellingShingle | Luis Sendra Gladys G. Olivera Rafael López-Andújar Cristina Serrano Luis E. Rojas Eva María Montalvá María José Herrero Salvador F. Aliño Pharmacogene Variants Associated with Liver Transplant in a Twelve-Year Clinical Follow-Up Pharmaceutics pharmacogenetics immunosuppressant ABC CYP SLCO |
| 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 | pharmacogenetics immunosuppressant ABC CYP SLCO |
| url | https://www.mdpi.com/1999-4923/14/2/354 |
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