SYSTEMATIC REVIEW article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders: Autoinflammatory Disorders
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1661502
Association of FCGR2A rs1801274 and FCGR3A rs396991 polymorphisms with various autoimmune diseases: A meta-analysis
Provisionally accepted
- 1Insitute of Translational Medicine, Faculty of Medical Sciences, Private University in the Principality of Liechtenstein, Triesen, Liechtenstein
- 2Institute of Clinical Epidemiology, Public Health, Health Economics, Medical Statistics and Informatics, Medical University of Innsbruck, Innsbruck, Austria
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Objectives: The aim of this systematic review with meta-analysis was to examine the association between the polymorphisms rs1801274 (FCGR2A-H131R) and rs396991 (FCGR3A-F158V) and susceptibility to autoimmune diseases (ADs), with a focus on the progress and novelty of studies published over the last two decades. Methods: A meta-analysis systematically evaluated FCGR2A/3A gene variants in autoimmune diseases (ADs) using four genetic models: dominant, recessive, overdominant, and allelic contrast. Results: The FCGR3A F158V polymorphism is significantly associated with immune thrombocytopenia in all four genetic models tested (dominant: OR = 2.67, 95% CI 1.94-3.67, for FV + VV vs. FF, recessive: OR = 2.38, 95% CI 1.78-3.19, for VV vs. FF + FV, overdominant: OR = 1.58, 95% CI 1.15-2.17, for FV vs. FF+VV, and allele comparison: OR = 1.97, 95% CI 1.70-2.29, for V vs. F, in the overall analyses). Statistically significant associations were also found between rheumatoid arthritis and FCGR3A F158V polymorphisms (recessive: OR = 1.36, 95% CI 1.09-1.69, for VV vs. FF + FV, and allele comparison: OR = 1.15, 95% CI 1.03-1.29, for V vs. F, in the overall analyses). Conversely, the overall analysis identified a negative association between the FCGR2A H131R polymorphism and rheumatoid arthritis in two genetic models (dominant: OR 0.83, 95% CI 0.69-1.00, for HR + RR vs. HH; allelic comparison: OR 0.86, 95% CI 0.76-0.97, for R vs. H). Conclusion: This meta-analysis reveals an association between FCGR3A V158 and an increased risk of immune thrombocytopenia and rheumatoid arthritis. However, this polymorphism is likely to explain only part of the pathogenesis of both diseases. Conversely, a protective association was found between FCGR2A R131 and rheumatoid arthritis. Nevertheless, the quantification of the total genetic contribution of a single gene remains challenging.
Keywords: FCGR2A, FCGR3a, Single nucleotide polymorphism, genetic variants, Autoimmune Diseases, Meta-analysis, Genetic association, Fc gamma receptor
Received: 07 Jul 2025; Accepted: 11 Aug 2025.
Copyright: © 2025 Thaler, Bublitz, Wipplinger, Gassner and Ulmer. 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: Elena Thaler, Insitute of Translational Medicine, Faculty of Medical Sciences, Private University in the Principality of Liechtenstein, Triesen, Liechtenstein
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