Interferon-induced transmembrane protein-3 genetic variant rs12252 is associated with COVID-19 mortality
Jahad Alghamdi, Manal Alaamery, Tlili Barhoumi, Mamoon Rashid, Hala Alajmi, Nasser Aljasser, Yaseen Alhendi, Hind Alkhalaf, Hanadi M. Alqahtani, Omer Algablan, Abdulraham I. Alshaya, Nabiha Tashkandi, Salam Massadeh, Bader Almuzzaini, Salleh N. Ehaideb, Mohammad Bosaeed, Kamal Ayoub, Saber Yezli, Anas Khan, Ahmed Alaskar, Abderrezak Bouchama
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.