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IFNG rs2430561 polymorphism and its association with disease onset, cutaneous severity, and activity in Vietnamese patients with lupus erythematosus

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Published: 22 September 2026
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Interferon (IFN)-γ plays a central role in lupus pathogenesis, and the IFNG rs2430561 (+874 T/A) polymorphism has been linked to systemic lupus erythematosus (SLE) in several populations. This study investigated the association of rs2430561 with disease onset, cutaneous severity, and global activity in Vietnamese patients with lupus erythematosus (LE). A case-control study was conducted on 34 LE patients and 34 age- and sex-matched healthy controls. Clinical characteristics, Cutaneous Lupus Disease Area and Severity Index (CLASI), and Systemic Lupus Erythematosus Disease Activity Index-2K (SLEDAI-2K) were collected. Genotyping was performed using allele-specific polymerase chain reaction (PCR). Genotype distribution differed significantly between patients and controls (p=0.048). Carriers of the A allele had a younger disease onset than TT patients (33.6±7.7 vs. 47.1±13.6 years) and showed a higher likelihood of onset ≤40 years (odds ratio [OR]=2.4; p=0.026). The rs2430561 genotype was associated with cutaneous severity: mean CLASI scores were AA 14.7, TA 11.8, and TT 5.8 (p=0.003). A-allele carriers had a 5.8-fold higher prevalence of severe CLASI (≥21; p=0.010). Systemic disease activity also differed: mean SLEDAI-2K scores were AA 12.0, TA 11.8, and TT 6.3 (p=0.010). The A allele was associated with a 4.7-fold higher prevalence of severe activity (>12; p=0.001). The IFNG rs2430561 A allele is associated with earlier onset and more severe cutaneous and systemic disease in Vietnamese LE patients, highlighting the potential contribution of IFN-γ pathway variation to disease expression.

 

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1. Psarras A, Emery P, Vital EM. Type I interferon-mediated autoimmune diseases: pathogenesis, diagnosis and targeted therapy. Rheumatology (Oxford) 2017;56:1662-75.
2. Ye L, Schnepf D, Staeheli P. Interferon-λ orchestrates innate and adaptive mucosal immune responses. Nat Rev Immunol 2019;19:614-25.
3. Ferber IA, Brocke S, Taylor-Edwards C, et al. Mice with a disrupted IFN-gamma gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE). J Immunol 1996;156:5-7.
4. Kim HJ, Eom CY, Kwon J, et al. Roles of interferon‐gamma and its target genes in schizophrenia: Proteomics‐based reverse genetics from mouse to human. Proteomics 2012;12:1815-29.
5. Liu W, Zhang S, Wang J. IFN-γ, should not be ignored in SLE. Front Immunol 2022;13:954706.
6. Sarangi S, Nahak SK, Padhi S, et al. Interferon-gamma (IFN-γ) intronic variant (rs2430561) is a risk factor for systemic lupus erythematosus: Observation from a meta-analysis. Lupus 2023;32:284-94.
7. Nakashima H, Inoue H, Akahoshi M, et al. The combination of polymorphisms within interferon-gamma receptor 1 and receptor 2 associated with the risk of systemic lupus erythematosus. FEBS Lett 1999;453:187-90.
8. Kim K, Cho SK, Sestak A, et al. Interferon-gamma gene polymorphisms associated with susceptibility to systemic lupus erythematosus. Ann Rheum Dis 2010;69:1247-50.
9. Tangwattanachuleeporn M, Sodsai P, Avihingsanon Y, et al. Association of interferon-gamma gene polymorphism (+874A) with arthritis manifestation in SLE. Clin Rheumatol 2007;26:1921-4.
10. Remmers EF, Plenge RM, Lee AT, et al. STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus. N Engl J Med 2007;357:977-86.
11. Santana-de Anda K, Gómez-Martín D, Monsivais-Urenda AE, et al. Interferon regulatory factor 3 as key element of the interferon signature in plasmacytoid dendritic cells from systemic lupus erythematosus patients: novel genetic associations in the Mexican mestizo population. Clin Exp Immunol 2014;178:428-37.
12. Wang JM, Huang AF, Yuan ZC, et al. Association of IRF5 rs2004640 polymorphism and systemic lupus erythematosus: A meta-analysis. Int J Rheum Dis 2019;22:1598-606.
13. Lessard CJ, Adrianto I, Ice JA, Wiley GB, et al; BIOLUPUS Network; GENLES Network. Identification of IRF8, TMEM39A, and IKZF3-ZPBP2 as susceptibility loci for systemic lupus erythematosus in a large-scale multiracial replication study. Am J Hum Genet 2012;90:648-60.
14. Zouali M. Epigenetics in lupus. Ann N Y Acad Sci 2011;1217:154-65.
15. López-Maderuelo D, Arnalich F, Serantes R, et al. Interferon-gamma and interleukin-10 gene polymorphisms in pulmonary tuberculosis. Am J Respir Crit Care Med 2003;167:970-5.
16. Liu S, Li J, Li Y, et al. Association Between the Interferon-γ +874 T/A Polymorphism and the Risk and Clinical Manifestations of Systemic Lupus Erythematosus: A Preliminary Study. Pharmgenomics Pers Med 2021;14:1475-82.
17. Al-Kholy W, Elsaid A, Sleem A, et al. TNF-α - 308 G > A and IFN-γ + 874 A > T gene polymorphisms in Egyptian patients with lupus erythematosus. Meta Gene 2016;9:137-41.
18. da Silva HD, da Silva AP, da Silva HA, et al. Interferon gamma and Interleukin 10 polymorphisms in Brazilian patients with systemic lupus erythematosus. Mol Biol Rep 2014;41:2493-500.
19. Apostolidis SA, Lieberman LA, Kis-Toth K, et al. The dysregulation of cytokine networks in systemic lupus erythematosus. J Interferon Cytokine Res 2011;31:769-79.
20. Aringer M. EULAR/ACR classification criteria for SLE. Semin Arthritis Rheum 2019;49:S14-7.
21. Ring J, Beyer K, Biedermann T, et al. Guideline (S2k) on acute therapy and management of anaphylaxis: 2021 update: S2k-guideline of the German society for allergology and clinical immunology (DGAKI), the medical association of German allergologists (AeDA), the society of pediatric allergology and environmental medicine (GPA), the German academy of allergology and environmental medicine (DAAU), the German professional association of pediatricians (BVKJ), the society for neonatology and pediatric intensive care (GNPI), the German society of dermatology (DDG), the Austrian society for allergology and immunology (ögai), the Swiss society for allergy and immunology (SGAI), the German society of anaesthesiology and intensive care medicine (DGAI), the German society of pharmacology (DGP), the German respiratory society (DGP), the patient organization German allergy and asthma association (DAAB), the German working group of anaphylaxis training and education (AGATE). Allergo J Int 2021;30:1-25.
22. Chakka S, Krain RL, Concha JSS, et al. The CLASI, a validated tool for the evaluation of skin disease in lupus erythematosus: a narrative review. Ann Transl Med 2021;9:431.
23. Touma Z, Urowitz MB, Gladman DD. SLEDAI-2K for a 30-day window. Lupus 2010;19:49-51.
24. Liu W, Li M, Wang Z, Wang J. IFN-γ Mediates the Development of Systemic Lupus Erythematosus. Biomed Res Int 2020;2020:7176515.
25. Eiamsitrakoon T, Tharabenjasin P, Pabalan N, et al. Influence of Interferon gamma+ 874 T> A (rs2430561) polymorphism on renal allograft rejection: A meta-analysis. Transplant Proc 2021;897-905.
26. Postal M, Vivaldo JF, Fernandez-Ruiz R, et al. Type I interferon in the pathogenesis of systemic lupus erythematosus. Curr Opin Immunol 2020;67:87-94.
27. Nicoletti F, Di Marco R, Zaccone P, et al. Dichotomic effects of IFN‐γ on the development of systemic lupus erythematosus‐like syndrome in MRL‐lpr/lpr mice. Eur J Immunol 2000;30:438-447.
28. Kantarci O, Goris A, Hebrink D, et al. IFNG polymorphisms are associated with gender differences in susceptibility to multiple sclerosis. Genes Immun 2005;6:153-61.
29. Sagwal S, Prasad R, Kaur J, Singh M. Cytokine signaling pathway in cystic fibrosis: expression of SOCS and STATs genes in different clinical phenotypes of the disease. Mol Cell Biochem 2021;476:2869-76.
30. Williams CL, Schilling MM, Cho SH, et al. STAT4 and T-bet are required for the plasticity of IFN-γ expression across Th2 ontogeny and influence changes in Ifng promoter DNA methylation. J Immunol 2013;191:678-87.
31. Reid S, Alexsson A, Frodlund M, et al. High genetic risk score is associated with early disease onset, damage accrual and decreased survival in systemic lupus erythematosus. Ann Rheum Dis 2020;79:363-9.
32. Vale ECSD, Garcia LC. Cutaneous lupus erythematosus: a review of etiopathogenic, clinical, diagnostic and therapeutic aspects. An Bras Dermatol 2023;98:355-72.
33. Pan Q, Chen J, Guo L, et al. Mechanistic insights into environmental and genetic risk factors for systemic lupus erythematosus. Am J Transl Res 2019;11:1241-54.
34. Duquia RP, Menezes AM, Almeida HL Jr, et al. Prevalence of sun exposure and its associated factors in southern Brazil: a population-based study. An Bras Dermatol 2013;88:554-61.
35. Bănescu C, Tripon F, Trifa AP, et al. Cytokine rs361525, rs1800750, rs1800629, rs1800896, rs1800872, rs1800795, rs1800470, and rs2430561 SNPs in relation with prognostic factors in acute myeloid leukemia. Cancer Med 2019;8:5492-506.
36. Chen J, Feng X, Desierto MJ, et al. IFN-γ-mediated hematopoietic cell destruction in murine models of immune-mediated bone marrow failure. Blood 2015;126:2621-31.
37. Wang X, Xia Y. Anti-double Stranded DNA Antibodies: Origin, Pathogenicity, and Targeted Therapies. Front Immunol 2019;10:1667.
38. Hodge DL, Berthet C, Coppola V, et al. IFN-gamma AU-rich element removal promotes chronic IFN-gamma expression and autoimmunity in mice. J Autoimmun 2014;53:33-45.
39. Braunstein I, Klein R, Okawa J, Werth VP. The interferon-regulated gene signature is elevated in subacute cutaneous lupus erythematosus and discoid lupus erythematosus and correlates with the cutaneous lupus area and severity index score. Br J Dermatol 2012;166:971-5.
40. Tofighi T, Morand EF, Touma Z. Systemic Lupus Erythematosus Outcome Measures for Systemic Lupus Erythematosus Clinical Trials. Rheum Dis Clin North Am 2021;47:415-26.
41. Gladman DD, Ibañez D, Urowitz MB. Systemic lupus erythematosus disease activity index 2000. J Rheumatol 2002;29:288-91.

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1.
IFNG rs2430561 polymorphism and its association with disease onset, cutaneous severity, and activity in Vietnamese patients with lupus erythematosus. Dermatol Reports [Internet]. 2026 Sep. 22 [cited 2026 Oct. 18];. Available from: https://journals.pagepress.net/dr/article/view/10886