Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Department of Internal Medicine, Ibrahim Badamasi Babangida Specialist Hospital, Minna, Nigeria.
Pharmacogenomics. 2024;25(7):329-341. doi: 10.1080/14622416.2024.2370761. Epub 2024 Aug 7.
Calcineurin inhibitors (CNIs) are the mainstay of immunosuppression in kidney transplantation. Interpatient variability in the disposition of calcineurin inhibitors is a well-researched phenomenon and has a well-established genetic contribution. There is great diversity in the makeup of African genomes, but very little is known about the pharmacogenetics of CNIs and transplant outcomes. This review focuses on genetic variants of calcineurin inhibitors' metabolizing enzymes (CYP3A4, CYP3A5), related molecules (POR, PPARA) and membrane transporters involved in the metabolism of calcineurin inhibitors. Given the genetic diversity across the African continent, it is imperative to generate pharmacogenetic data, especially in the era of personalized medicine and emphasizes the need for studies specific to African populations. The study of allelic variants in populations where they have greater frequencies will help answer questions regarding their impact. We aim to fill the knowledge gaps by reviewing existing research and highlighting areas where African research can contribute.
钙调磷酸酶抑制剂(CNIs)是肾移植中免疫抑制的主要药物。钙调磷酸酶抑制剂的处置在患者间存在可变性,这是一个经过充分研究的现象,具有明确的遗传贡献。非洲基因组的组成存在很大的多样性,但关于 CNI 及其移植结果的药物遗传学知之甚少。本综述重点介绍了钙调磷酸酶抑制剂代谢酶(CYP3A4、CYP3A5)、相关分子(POR、PPARA)和参与钙调磷酸酶抑制剂代谢的膜转运体的遗传变异。鉴于非洲大陆的遗传多样性,必须生成药物遗传学数据,尤其是在个性化医疗时代,这强调了需要针对非洲人群进行研究。在这些等位基因变异在人群中更为常见的地区进行研究,将有助于回答它们的影响问题。我们旨在通过回顾现有研究并强调非洲研究可以做出贡献的领域来填补知识空白。