Brief Communication
  

Association between IFN‐γ +874T/A SNP and COVID-19 Severity

Abstract

The severity of coronavirus disease 2019 (COVID-19) varies significantly among individuals, which indicates the impact of individual differences on disease. Emerging evidence suggests that genetic factors play a crucial role in determining the severity of the disease. For instance, variants in the interferon-gamma (IFN-γ) gene, such as the +874 T/A single nucleotide polymorphism (SNP), have been linked to altered immune responses and may influence the severity of COVID-19. We aim to determine the influence of the IFN‐γ +874T/A SNP on the clinical outcomes of COVID-19 patients.
We investigated the SNP at position +874 in the promoter region of the IFN-γ gene in 416 individuals (206 critically ill COVID-19 patients and 210 healthy controls) in northwestern of Iran. Genomic DNA was extracted from the blood leukocytes of the patients, and the SNP was analyzed using the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) method.
The AA genotype was significantly more frequent in critically ill COVID-19 patients than in healthy controls. Conversely, the AT and TT genotypes were more common in healthy controls. Furthermore, the A allele was more frequent in critically ill patients than in healthy controls, while the T allele was more frequent in healthy controls compared to critically ill patients.
Our study identified the IFN-γ +874T/A SNP as a significant genetic factor influencing COVID-19 severity. This finding underscores the critical role of genetic factors in disease severity and highlights the importance of personalized medicine in managing COVID-19.

1. Li H, Liu SM, Yu XH, Tang SL, Tang CK. Coronavirus disease 2019 (COVID-19): current status and future perspectives. Int J Antimicrob Agents. 2020;55(5):105951.
2. Srivastava P, Gupta N. Clinical manifestations of corona virus disease. Clinical Synopsis of COVID-19: Evolving and Challenging. 2020:31-49.
3. van der Made CI, Netea MG, van der Veerdonk FL, Hoischen A. Clinical implications of host genetic variation and susceptibility to severe or critical COVID-19. Genome Med. 2022;14(1):96.
4. Kak G, Raza M, Tiwari BK. Interferon-gamma (IFN-γ): Exploring its implications in infectious diseases. Biomol Concepts. 2018;9(1):64-79.
5. Coperchini F, Chiovato L, Croce L, Magri F, Rotondi M. The cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system. Cytokine Growth Factor Rev. 2020;53(14):25-32.
6. Xu H, Li W, Fu H, Jiang G. Interferon-gamma gene polymorphism+ 874 (A/T) in Chinese children with Henoch-Schönleinpurpura. Iran J Allergy Asthma Immunol. 2014:184-9.
7. Zhang Y, Qin L, Zhao Y, Zhang P, Xu B, Li K, et al. Interferon-induced transmembrane protein 3 genetic variant rs12252-C associated with disease severity in coronavirus disease 2019. J Infect Dis. 2020;222(1):34-7.
8.Farhat K, Hassen E, Gabbouj S, Bouaouina N, Chouchane L. Interleukin‐10 and interferon‐gamma gene polymorphisms in patients with nasopharyngeal carcinoma. Int J Immunogenetics. 2008;35(3):197-205.
9. Ivashkiv LB. IFNγ: signalling, epigenetics and roles in immunity, metabolism, disease and cancer immunotherapy. Nat Rev Immunol. 2018;18(9):545-58.
10. Sarges KM, Póvoa da Costa F, Santos EF, Cantanhede MH, da Silva R, et al. Association of the IFNG+ 874T/A Polymorphism with Symptomatic COVID-19 Susceptibility. Viruses. 2024;16(4):650.
11. Castro F, Cardoso AP, Gonçalves RM, Serre K, Oliveira MJ. Interferon-gamma at the crossroads of tumor immune surveillance or evasion. Fron Immunol. 2018;9(3):847.
12. Teker E, Akadam-Teker AB, Ozturk O, Eronat AP, Yalin K, Golcuk SE, et al. Association between the interferon gamma 874 T/A polymorphism and the severity of valvular damage in patients with rheumatic heart disease. Biochem Genetics. 2018;56(12):225-34.
13. Vu D, Shah T, Ansari J, Sakharkar P, Yasir Q, Naraghi R, Hutchinson I, Min D. Interferon‐gamma gene polymorphism+ 874 A/T is associated with an increased risk of cytomegalovirus infection among Hispanic renal transplant recipients. Trans Infect Dis. 2014;16(5):724-32.
14. Dieter C, Brondani LD, Leitão CB, Gerchman F, Lemos NE, Crispim D. Genetic polymorphisms associated with susceptibility to COVID-19 disease and severity: A systematic review and meta-analysis. PLoS One. 2022;17(7):e0270627.
Files
IssueVol 24 No 2 (2025) QRcode
SectionBrief Communication
Keywords
COVID-19 IFN‐γ Polymorphism SARS-CoV-2
Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Seyyed rezaei SA, Asgharzadeh V, Mahdavi Poor B, Asgharzadeh M, Poorghani A, Asghari Ozma M, Khalili A, Jalaei Nobari H, Raeisi M, Rashedi J. Association between IFN‐γ +874T/A SNP and COVID-19 Severity. Iran J Allergy Asthma Immunol. 2025;24(2):254-258.