Tsironi Anna, Lazaros Konstantinos, Mendrinou Effrosyni, Papasotiriou Marios, Siamoglou Stavroula, Kydonopoulou Kyriaki, John Anne, Gerou Alexandra, Gerou Spyridon, Ali Bassam R, Vrahatis Aristidis G, Patrinos George P
Laboratory of Pharmacogenomics and Individualized Therapy, Division of Pharmacology and Biosciences, Department of Pharmacy, School of Health Sciences, University of Patras, Patras, Greece.
Department of Informatics, Ionian University, Corfu, Greece.
Front Pharmacol. 2025 Mar 19;16:1538432. doi: 10.3389/fphar.2025.1538432. eCollection 2025.
Tacrolimus, an approved first-line calcineurin inhibitor, is widely prescribed in organ transplantation to prevent allograft rejection. Its narrow therapeutic index requires precise management to achieve optimal dosing and to minimize adverse drug events (ADEs) while ensuring its therapeutic efficacy. Among several factors, genetic differences contribute significantly to the inter-individual and inter-ethnic variability in pharmacokinetics (PK) of tacrolimus in kidney transplant recipients. As a result, investigating the role of genetic variation in Greek transplant recipients becomes crucial to optimizing therapeutic strategies and enhancing the efficacy of immunosuppressive treatment.
Genetic variants which are known to influence the activity of enzymes or drug-transporters critical to tacrolimus pharmacokinetics, may significantly affect the required kidney post-transplant tacrolimus daily dose.
To assess the correlation of genetic variants (rs1128503, rs2229109) and (rs2242480, rs4986910) with tacrolimus dose-adjusted trough concentration (C/D), in Greek kidney transplant recipients.
Ninety-four unrelated Greek kidney transplant recipients were included in this study from the Department of Nephrology and Kidney Transplantation of the University General Hospital of Patras. Patients' dose-adjusted trough levels were measured at five distinct time points after transplantation and analyzed in relation to the possible influence of and correlated with the abovementioned genetic variants using standard genotyping analysis and Sanger sequencing.
The genetic variants rs1128503, rs2229109, rs2242480, rs4986910 did not show any significant association with the daily dosing requirements of tacrolimus for at least 1 year, in Greek patients who have undergone kidney transplant.
It remains uncertain whether these genetic variants influence the assessment of the appropriate tacrolimus dosing 1 year after transplantation in Greek kidney transplant recipients.
他克莫司是一种已获批的一线钙调神经磷酸酶抑制剂，在器官移植中被广泛用于预防同种异体移植排斥反应。其治疗指数狭窄，需要精确管理以实现最佳给药，并在确保治疗效果的同时将药物不良事件（ADEs）降至最低。在多个因素中，基因差异对肾移植受者他克莫司药代动力学（PK）的个体间和种族间变异性有显著影响。因此，研究希腊移植受者基因变异的作用对于优化治疗策略和提高免疫抑制治疗效果至关重要。
已知影响对他克莫司药代动力学至关重要的酶或药物转运体活性的基因变异，可能会显著影响肾移植后所需的他克莫司每日剂量。
评估希腊肾移植受者中基因变异（rs1128503、rs2229109）和（rs2242480、rs4986910）与他克莫司剂量调整后的谷浓度（C/D）的相关性。
本研究纳入了来自帕特雷大学综合医院肾脏病与肾移植科的94名无亲缘关系的希腊肾移植受者。在移植后的五个不同时间点测量患者的剂量调整后的谷浓度，并分析其与上述基因变异可能的影响，并使用标准基因分型分析和桑格测序与上述基因变异进行关联分析。
在接受肾移植的希腊患者中，基因变异rs1128503、rs2229109、rs2242480、rs4986910与他克莫司至少1年的每日给药需求均未显示出任何显著关联。
这些基因变异是否会影响希腊肾移植受者移植后1年他克莫司合适剂量的评估仍不确定。
