Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 24 2 2025 03 10 254 258 Seyyed Amin Seyyed rezaei Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran Vahid Asgharzadeh Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran Behroz Mahdavi Poor Infectious and Tropical Diseases Research Center, Faculty of Paramedicine, Tabriz University of Medical Sciences, Tabriz, Iran Mohammad Asgharzadeh Biotechnology Research Center, Faculty of Paramedicine, Tabriz University of Medical Sciences, Tabriz, Iran Asra Poorghani Biotechnology Research Center, Faculty of Paramedicine, Tabriz University of Medical Sciences, Tabriz, Iran Mahdi Asghari Ozma Drug Applied Research Center, Tabriz university of Medical Sciences, Tabriz, Iran Ahmad Khalili Department of Cardiovascular Surgery, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran Hossein Jalaei Nobari Department of Islamic Education, Faculty of Paramedicine, Tabriz University of Medical Sciences, Tabriz, Iran Mortaza Raeisi Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Jalil Rashedi Department of Laboratory Sciences, Faculty of Paramedicine, Tabriz University of Medical Sciences, Tabriz, Iran 2024 08 13 2024 12 01 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. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4176 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4176/2165