Kotowska Katarzyna, Wojciuk Bartosz, Sieńko Jerzy, Bogacz Anna, Stukan Iga, Drożdżal Sylwester, Czerny Bogusław, Tejchman Karol, Trybek Grzegorz, Machaliński Bogusław, Kotowski Maciej
Clinic of Maxillofacial Surgery, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland.
Department of Immunological Diagnostics, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland.
J Clin Med. 2024 Aug 22;13(16):4966. doi: 10.3390/jcm13164966.
Kidney transplantation is followed by immunosuppressive therapy involving calcineurin inhibitors (CNIs) such as cyclosporin A. However, long-term high CNIs doses can lead to vitamin D deficiency, and genetic variations influencing vitamin D levels can indirectly impact the necessary CNIs dosage. This study investigates the impact of genetic variations of vitamin D binding protein () rs2282679 and hydroxylase rs10741657 polymorphisms on the cyclosporin A dosage in kidney transplant recipients. Additional polymorphisims of genes that are predicted to influence the pharmacogenetic profile were included. Gene polymorphisms in 177 kidney transplant recipients were analyzed using data mining techniques, including the Random Forest algorithm and Classification and Regression Trees (C&RT). The relationship between the concentration/dose (C/D) ratio of cyclosporin A and genetic profiles was assessed to determine the predictive value of rs2282679 and rs10741657 polymorphisms. Polymorphic variants of the (rs2282679) demonstrated a strong predictive value for the cyclosporin A C/D ratio in post-kidney transplantation patients. By contrast, the polymorphism (rs10741657) did not show predictive significance. Additionally, the immune response genes rs231775 and rs1800896 were identified as predictors of cyclosporin A response, though these did not result in statistically significant differences. rs2282679 polymorphisms can significantly predict the cyclosporin A C/D ratio, potentially enhancing the accuracy of CNI dosing. This can help identify patient groups at risk of vitamin D deficiency, ultimately improving the management of kidney transplant recipients. Understanding these genetic influences allows for more personalized and effective treatment strategies, contributing to better long-term outcomes for patients.
肾移植术后需进行免疫抑制治疗，其中包括使用钙调神经磷酸酶抑制剂（CNIs），如环孢素A。然而，长期高剂量的CNIs会导致维生素D缺乏，而影响维生素D水平的基因变异会间接影响所需的CNIs剂量。本研究调查了维生素D结合蛋白（）rs2282679和羟化酶rs10741657基因多态性对肾移植受者环孢素A剂量的影响。还纳入了预计会影响药物遗传学特征的其他基因多态性。使用数据挖掘技术，包括随机森林算法和分类与回归树（C&RT），对177名肾移植受者的基因多态性进行了分析。评估环孢素A浓度/剂量（C/D）比值与基因谱之间的关系，以确定rs2282679和rs10741657基因多态性的预测价值。（rs2282679）的多态性变体对肾移植术后患者的环孢素A C/D比值具有很强的预测价值。相比之下，多态性（rs10741657）未显示出预测意义。此外，免疫反应基因rs231775和rs1800896被确定为环孢素A反应的预测因子，尽管这些结果没有统计学上的显著差异。rs2282679基因多态性可以显著预测环孢素A的C/D比值，有可能提高CNIs给药的准确性。这有助于识别有维生素D缺乏风险的患者群体，最终改善肾移植受者的管理。了解这些基因影响有助于制定更个性化、有效的治疗策略，为患者带来更好的长期预后。
