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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| Main Authors: | , , , , , , , |
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| Format: | Book |
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MDPI AG,
2022-02-01T00:00:00Z.
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| Summary: | 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. |
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| Item Description: | 10.3390/pharmaceutics14020354 1999-4923 |