REVIEW article
Front. Genet.
Sec. Pharmacogenetics and Pharmacogenomics
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1594648
This article is part of the Research TopicAdvancements in Biomarker Genetics: Insights from the Genomics EraView all 3 articles
Gene Polymorphisms Associated with Immunosuppressant Adverse Effects in Systemic Lupus Erythematosus: A Narrative Review
Provisionally accepted
- 1Department of Biological Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, Indonesia
- 2Rheumatology Division, Department of Internal Medicine, Faculty of Medicine, Universitas Padjadjaran, Hasan Sadikin Hospital, Bandung, West Java, Indonesia
- 3Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Bandung, West Java, Indonesia
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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 (MTHFR and ATIC), AZA (TPMT, NUDT15, ITPA, ABCC4), CYC (CYP2C19, GSTM1, GSTT1, GSTP1, ALDH), and MMF (SLCO1B1, IMPDH1, UGT2B7). 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.
Keywords: Single nucleotide polymorphism, adverse effect, Methotrexate, Azathioprine, Cyclophosphamide, Mycophenolate mofetil
Received: 20 Mar 2025; Accepted: 29 May 2025.
Copyright: © 2025 Hamdani, Hamijoyo, Amalia and Barliana. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Melisa Intan Barliana, Department of Biological Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, Indonesia
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