The IFIH1 gene variants rs1990760 and rs2111485 are associated with COVID-19 susceptibility and affect IFIH1 protein levels in Iraqis.

Background: Interferon-induced helicase C domain-containing protein 1 (IFIH1) is one of the main pattern recognition receptors that sense viral RNA and activate host cells to mount an effective antiviral immunity. Methods: A case–control study (90 patients with mild/moderate COVID-19 and 90 matched controls) was performed to explore the association of two variants of the IFIH1 gene with COVID-19 risk using the tetra-primer amplification refractory mutation system-polymerase-chain-reaction method. The first is a missense variant, rs1990760 C/T, and the second is an intergenic variant, rs2111485 A/G. In addition, serum IFIH1 levels were assessed using an ELISA kit. Results: Mutant alleles (T and G, respectively) and corresponding homozygous genotypes (TT and GG, respectively) of both variants were significantly associated with increased risk of COVID-19. IFIH1 levels were significantly higher in patients compared to controls and were favorably affected by the rs1990760 and rs2111485 mutant-type genotypes. Conclusion: IFIH1 protein showed up-regulated levels in the serum of patients with mild/moderate COVID-19. In addition, the IFIH1 gene variants rs1990760 C/T and rs2111485 A/G were associated with susceptibility to COVID-19, and the study suggests that their mutant-type genotypes are not only associated with increased risk of COVID-19 but also contributed to higher serum IFIH1 levels. [ABSTRACT FROM AUTHOR]