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

Abstract

Interferon-induced membrane proteins (IFITM) 3 gene variants are known risk factor for severe viral diseases. We examined whether IFITM3 variant may underlie the heterogeneous clinical outcomes of SARS-CoV-2 infection-induced COVID-19 in large Arab population . We genotyped 880 Saudi patients; 93.8% were PCR-confirmed SARS-CoV-2 infection, encompassing most COVID-19 phenotypes. Mortality at 90 days was 9.1%. IFITM3-SNP, rs12252-G allele was associated with hospital admission (OR = 1.65 [95% CI; 1.01–2.70], P = 0.04]) and mortality (OR = 2.2 [95% CI; 1.16–4.20], P = 0.01). Patients less than 60 years old had a lower survival probability if they harbor this allele (log-rank test P = 0.002). Plasma levels of IFNγ were significantly lower in a subset of patients with AG/GG genotypes than patients with AA genotype ( P = 0.00016). Early identification of these individuals at higher risk of death may inform precision public health response.

Association between the interferon-induced transmembrane protein 3 gene (IFITM3) rs34481144 / rs12252 haplotypes and COVID-19

“…Zhang et al compared 56 mild and 24 severe COVID-19 patients and found a higher frequency of the GG homozygotes among the severe cases (Zhanget al, 2020). In a study involving 880 Saudi patients, Alghamdi et al found that rs12252-G was associated with hospital admission (OR = 1.65; 95% CI = 1.01–2.70) and mortality (OR = 2.2; 95% CI = 1.16–4.20) ( Alghamdi et al, 2021 ). Our group also found a significantly higher frequency of the rs12252-G among COVID-19 patients who required hospitalization (n = 288) during the first pandemic wave (march–may 2020) in Spain, compared to age and sex matched population controsl (n = 440) (Gomez et al, 2021).…”

“…In agreement with this role in infection, variants in the IFITM3 gene have been associated with the clinical outcomes after SARS-CoV-2 infection (COVID-19). Most of the studies analysed the rs12252 SNP and concluded an association between the G allele and disease severity or a lack of association, but were based on small sizes that impairs the statistical power ( Zhang et al, 2020 ; Schönfelder et al, 2021 ; Gómez et al, 2021 ; Alghamdi et al, 2021 ).…”

Update on human genetic susceptibility to COVID-19: susceptibility to virus and response

“…Variants of the TLR7 gene are associated with the immune response against single-stranded RNA virus and to the onset of autoimmune disease such as systemic lupus erythematosus (SLE) [47]. Several scientific contributions focused on the potential relevance of HLA complex polymorphisms for SARS-CoV-2 susceptibility (Table 1) [23,[48][49][50][51][52][53][54][55][56][57][58] and for the disease severity extent [59].…”

Human Genetic Polymorphisms Associated with Susceptibility to COVID-19 Infection and Response to Treatment

“…In a study investigating gene polymorphisms in the pentraxin 3 (PTX3), a molecule that is synthesized by a number of inflammatory cells and considered to be associated with mortality, MAS was found to be less common in COVID-19 patients with the AG genotype (rs1840680 (1449A/G) polymorphism) and PTX3 levels were higher in patients carrying the A allele [103]. In a study on interferon-induced membrane protein-3 (IFITM-3) gene variants, an established risk factor in severe viral infections, the IFITM3-SNP, rs12252-G allele was found to be significantly associated with hospitalization and mortality in COVID-19 patients and lower IFNγ levels were lower patients with the AG/GG genotype [105]. Homocysteine can be used as a potential biomarker to predict the severity of a number of infections in COVID-19.…”