Shahed University Immunoregulation 2588_5200 8 1 2025 01 01 Association of Transmembrane Immunoglobulin and Mucin Domain rs10515746 Polymorphism With Severity and Mortality of COVID-19 in the Iranian Population 5050 10.32598/Immunoregulation.8.17 EN Ensie Sadat Mirsharif Immunoregulation Research Center, Shahed University, Tehran, Iran. 0000-0002-6271-491X Abdolrahman Rostamian Rheumatology Research Center, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran. Mohammadreza Salehi Department of Infectious and Tropical Medicines, Tehran University of Medical Sciences, Tehran, Iran. Nayere Askari Immunoregulation Research Center, Shahed University, Tehran, Iran. 0000-0002-2966-3954 Tooba Ghazanfari Immunoregulation Research Center, Shahed University, Tehran, Iran. 0000-0002-1049-7095 Journal Article 2025 10 01 <strong>Background</strong>: T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) is an inhibitory immune checkpoint regulating T cell immune responses. This study aimed to evaluate the association between the TIM-3 rs10515746 single-nucleotide polymorphism and the severity and mortality of coronavirus disease 2019 (COVID-19) among Iranians.<br /><strong>Materials and Methods: </strong>Genomic DNA was extracted from peripheral blood nucleated cells of 828 COVID-19 patients and 166 healthy controls without COVID-19. The TIM-3 polymorphic site was analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. To determine whether genetic variation was associated with hepatitis A virus cellular receptor 2 (HAVCR-2) messenger ribonucleic acid (mRNA) expression, total RNA was extracted from 175 COVID-19 patients and 65 healthy controls, and HAVCR-2 expression levels were quantified using reverse transcription-polymerase chain reaction (RT-PCR). <br /><strong>Results</strong>: The genotypic frequencies of TIM-3 574A>C (rs10515746) polymorphism were in accordance with the Hardy-Weinberg equilibrium in the healthy control subjects (P>0.05). No significant difference was observed in their distribution frequencies of rs10515746 between the genotypes and alleles among COVID-19 patients vs. controls, inpatients vs outpatients, intensive care unit (ICU) vs non-ICU admitted patients, and survivors vs. non-survivors under different genetic models. Also, no significant difference was observed in the mRNA expression of HAVCR-2 in COVID-19 patients with other genotypes.<br /><strong>Conclusion</strong>: COVID-19 infection was not associated with the TIM-3 574A>C (rs10515746) polymorphism among the Iranians. https://immunoreg.shahed.ac.ir/article_5050_8977ecbb8cb82d77fb091c7a7f186163.pdf