Association of Transmembrane Immunoglobulin and Mucin Domain rs10515746 Polymorphism With Severity and Mortality of COVID-19 in the Iranian Population

Background: 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.
Materials and Methods: 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). 
Results: 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.
Conclusion: COVID-19 infection was not associated with the TIM-3 574A>C (rs10515746) polymorphism among the Iranians.