Hamdani Siva, Hamijoyo Laniyati, Amalia Riezki, Barliana Melisa I
Department of Biological Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, Indonesia.
Unit of Pharmacology, Clinical Pharmacy and Community, Faculty of Science, Universitas Garut, Garut, Indonesia.
Front Genet. 2025 Jun 24;16:1594648. doi: 10.3389/fgene.2025.1594648. eCollection 2025.
Systemic Lupus Erythematosus (SLE) is an autoimmune disease that often requires treatment with immunosuppressant drugs to manage symptoms and prevent organ damage. However, the use of immunosuppressant can be associated with various adverse effects. The spectrum of immunosuppressant toxicity is influenced by various factors such as organ function and medication interval, but genetic variations-particularly single nucleotide polymorphisms-have emerged as critical determinants due to their direct impact on the drug's pharmacokinetics and pharmacodynamics alteration, also on patient susceptibility to adverse reactions. This review summarizes the current knowledge on gene polymorphisms associated with immunosuppressant adverse effects in SLE patients, focusing on commonly used drugs such as Methotrexate (MTX), Azathioprine (AZA), Cyclophosphamide (CYC), and Mycophenolate Mofetil (MMF). A total of 23 relevant studies published in the last decade were identified through a comprehensive literature search, specifically investigating the relationship between gene polymorphisms and adverse drug reactions in SLE patients. The findings reveal that gene polymorphisms are frequently associated with adverse effects for each immunosuppressant, including MTX ( and ), AZA (), CYC (), and MMF (). Understanding the functional implications of these gene polymorphisms contributes to the application of precision medicine, as they can serve as potential markers for drug selection and dosage adjustment during initiation treatment of immunosuppressant to enhance treatment efficacy, minimize toxicity, and improve outcomes for SLE patients.
系统性红斑狼疮(SLE)是一种自身免疫性疾病,通常需要使用免疫抑制剂进行治疗以控制症状并预防器官损伤。然而,免疫抑制剂的使用可能会带来各种不良反应。免疫抑制剂毒性的范围受到多种因素的影响,如器官功能和用药间隔,但基因变异——尤其是单核苷酸多态性——已成为关键决定因素,因为它们直接影响药物的药代动力学和药效学改变,也影响患者对不良反应的易感性。本综述总结了目前关于SLE患者中与免疫抑制剂不良反应相关的基因多态性的知识,重点关注常用药物,如甲氨蝶呤(MTX)、硫唑嘌呤(AZA)、环磷酰胺(CYC)和霉酚酸酯(MMF)。通过全面的文献检索,共确定了过去十年发表的23项相关研究,具体研究了SLE患者基因多态性与药物不良反应之间的关系。研究结果表明,基因多态性通常与每种免疫抑制剂的不良反应相关,包括MTX(和)、AZA()、CYC()和MMF()。了解这些基因多态性的功能意义有助于精准医学的应用,因为它们可以作为免疫抑制剂初始治疗期间药物选择和剂量调整的潜在标志物,以提高治疗效果、最小化毒性并改善SLE患者的预后。