Genetic polymorphisms associated with therapeutic response and adverse effects to methotrexate in Taiwanese patients with rheumatoid arthritis: a real-world, hospital-based study.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος:	Genetic polymorphisms associated with therapeutic response and adverse effects to methotrexate in Taiwanese patients with rheumatoid arthritis: a real-world, hospital-based study.
Συγγραφείς:	Yu TW; Department of Internal medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC., Chen IC; Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan, ROC.; Master Program in Precision Health, National Chung Hsing University, Taichung, Taiwan, ROC., Lin GC; Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan, ROC., Kao CM; Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan, ROC.; Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, 1650 Taiwan Boulevard, Section 4, Xitun Dist, Taichung City, 407, Taiwan., Chen YJ; Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan, ROC.; Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, 1650 Taiwan Boulevard, Section 4, Xitun Dist, Taichung City, 407, Taiwan., Chen YM; Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan, ROC. ymchen1@vghtc.gov.tw.; Graduate Institute of Clinical Medicine, National Chung-Hsing University, Taichung, Taiwan, ROC. ymchen1@vghtc.gov.tw.; School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan, ROC. ymchen1@vghtc.gov.tw.; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung-Hsing University, Taichung, Taiwan, ROC. ymchen1@vghtc.gov.tw.; Precision Medicine Research Center, College of Medicine, National Chung Hsing University, Taichung, Taiwan, ROC. ymchen1@vghtc.gov.tw.; Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, 1650 Taiwan Boulevard, Section 4, Xitun Dist, Taichung City, 407, Taiwan. ymchen1@vghtc.gov.tw.
Πηγή:	Scientific reports [Sci Rep] 2026 Jun 09; Vol. 16 (1). Date of Electronic Publication: 2026 Jun 09.
Τύπος έκδοσης:	Journal Article
Γλώσσα:	English
Στοιχεία περιοδικού:	Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
Imprint Name(s):	Original Publication: London : Nature Publishing Group, copyright 2011-
Ιατρικοί όροι (MeSH):	Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/genetics , Methotrexate/adverse effects , Methotrexate/therapeutic use , Antirheumatic Agents/adverse effects , Antirheumatic Agents/therapeutic use , Polymorphism, Single Nucleotide*, ATP-Binding Cassette, Sub-Family C Proteins/genetics ; Humans ; Taiwan ; Female ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Aged
Περίληψη:	Although methotrexate (MTX) is extensively utilized in management of rheumatoid arthritis (RA), its pharmacogenomics are still unclear. This study explores the genetic determinants impacting MTX's effectiveness and adverse effects in Taiwanese patients with RA, aiming to enhance understanding of RA treatment and pharmacogenetics. A retrospective analysis of 1,948 RA patients receiving MTX treatment from January 2009 to January 2022, using data from the Taiwan Precision Medicine Initiative (TPMI) at Taichung Veterans General Hospital. Among these patients, 872 who required treatment with biologic disease modifying anti-rheumatic drugs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) were classified as MTX 'non-response', while the 1,076 patients treated without these agents were categorized as MTX 'response'. Chi-square analysis was employed to compare the carrier ratio of 82 selected MTX-associated SNPs from previous literature. Logistic regression models were utilized to explore associations between genetic variants and the risk of non-response and adverse effects, with adjustments made for potential confounding factors. Significant genetic markers influencing MTX response included ABCC1 rs212090, which predicted better MTX efficacy (p = 0.016), and ABCC3 rs2277624 and rs4148416, linked to lower MTX response rates (p = 0.004 and p = 0.023). SNPs in ADORA3 rs2298191 and ABCC4 rs7317112 were linked to a higher risk of thrombocytopenia (p = 0.045 and p = 0.049). Our study identifies genetic variations ABCC1 and ABCC3 related to MTX efficacy in treating RA, while SNPs in ADORA3 and ABCC4 are associated with the side effect of thrombocytopenia. These insights offer a foundation for tailoring individual treatment plans based on genetic profiles. (© 2026. The Author(s).)
Competing Interests:	Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: All individual in this study afforded written informed consent, and the research protocol was duly permitted by the ethics committee of the Institutional Review Board at TCVGH (IRB No. SF19153A).
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Grant Information:	TCVGH-1127301C, TCVGH-1127302D, TCVGH-YM1120110, TCVGH-1137310C, TCVGH-1137319C, TCVGH-1137302D, TCVGH-1127304B, TCVGH-1137302B, and TCVGH-1143903B Taichung Veterans General Hospital; NSTC -111-2634-F-A49-014, NSTC-111-2218-E-039-001, and NSTC-111-2314-B-075A-003-MY3 National Science and Technology Council; 40-05-GMM and AS-GC-110-MD0 Academia Sinica
Contributed Indexing:	Keywords: Adverse drug effects; Disease-modifying antirheumatic drugs; Methotrexate; Pharmacogenetics; Rheumatoid arthritis; Single nucleotide polymorphisms; Treatment efficacy
Substance Nomenclature:	YL5FZ2Y5U1 (Methotrexate) 0 (Antirheumatic Agents) 0 (ATP-Binding Cassette, Sub-Family C Proteins) Y49M64GZ4Q (multidrug resistance-associated protein 1)
Entry Date(s):	Date Created: 20260609 Date Completed: 20260820 Latest Revision: 20260823
Update Code:	20260823
PubMed Central ID:	PMC13493981
DOI:	10.1038/s41598-026-54386-3
PMID:	42265358
Βάση Δεδομένων:	MEDLINE

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Περιγραφή
ISSN:	2045-2322
DOI:	10.1038/s41598-026-54386-3