The Functional OAS1 rs10774671A>G Variant Is Associated with COVID-19 Susceptibility in Mexican Patients

OAS1 (2'-5'-oligoadenylate synthetase 1) and OAS3 have been identified through a genome-wide association study as major loci associated with COVID-19. The rs10774671A>G variant affects alternative splicing and generates two distinct mRNA and protein isoforms. The A allele produces the shorter p42 isoform, which has been associated with increased susceptibility, greater disease severity, and higher mortality from COVID-19, whereas the G allele produces the longer p46 isoform, which has been associated with a protective effect. In addition, the functional variants OAS1 rs4767027C>T, OAS1 rs1131454A>G, and OAS3 rs10735079A>G have also been associated with susceptibility to and/or severity of COVID-19. Therefore, the aim of this study was to determine whether four variants in the OAS1 and OAS3 genes are associated with susceptibility to COVID-19 and with the clinical signs and symptoms of the disease. We included 305 patients with COVID-19 and 288 healthy controls. We genotyped the OAS1 rs10774671A>G, rs4767027C>T, rs1131454A>G, and OAS3 rs10735079A>G variants using TaqMan^® assays. The association between OAS1 and OAS3 variants and disease susceptibility or severity was assessed using binary logistic regression adjusted for age and sex. The Hardy-Weinberg equilibrium was evaluated using SNPStats, whereas haplotypes and linkage disequilibrium were analyzed with Haploview. Statistical power was calculated using Quanto. Logistic regression analysis adjusted for age and sex revealed an association between the OAS1 rs10774671A risk allele and susceptibility to COVID-19 (G vs. A: OR = 1.9, p = 0.007). In contrast, no associations with COVID-19 susceptibility were observed for the rs4767027C>T, rs1131454A>G, or rs10735079A>G variants. However, the rs1131454A>G and rs10735079A>G variants showed associations with sore throat. Overall, our findings suggest that OAS1 acts as a susceptibility factor for COVID-19 and the rs1131454A>G and rs10735079A>G SNVs are associated with sore throat in the Mexican population.