Interferon-induced transmembrane protein-3 genetic variant rs12252 is associated with COVID-19 mortality

Area of Science:

• Genetics
• Immunology
• Infectious Diseases

Background:

• Interferon-induced membrane protein 3 (IFITM3) gene variants are recognized risk factors for severe viral infections.
• The clinical presentation of SARS-CoV-2 infection varies significantly, suggesting underlying genetic influences.

Purpose of the Study:

• To investigate the association between IFITM3 gene variants and the diverse clinical outcomes of COVID-19 in a large Saudi Arabian population.
• To determine if a specific IFITM3 variant correlates with disease severity, hospital admission, and mortality.

Main Methods:

• Genotyping of the IFITM3 gene (specifically SNP rs12252) in 880 Saudi patients with confirmed SARS-CoV-2 infection.
• Analysis of clinical data, including hospital admission, mortality at 90 days, and plasma levels of Interferon-gamma (IFNγ).
• Statistical analysis including odds ratios (OR), confidence intervals (CI), P-values, and log-rank tests to assess associations.

Main Results:

• The rs12252-G allele of the IFITM3 gene was significantly associated with increased hospital admission (OR = 1.65, P = 0.04) and mortality (OR = 2.2, P = 0.01).
• Patients under 60 years old carrying the rs12252-G allele exhibited a lower survival probability (P = 0.002).
• Lower plasma levels of IFNγ were observed in patients with AG/GG genotypes compared to AA genotypes (P = 0.00016).

Conclusions:

• The IFITM3 rs12252-G allele is a significant genetic risk factor for severe COVID-19 outcomes in the Saudi population.
• This finding highlights the role of IFITM3 in modulating the immune response to SARS-CoV-2.
• Identifying individuals with this allele could enable targeted public health interventions for high-risk populations.