Associations Between IFI44L Gene Variants and Rates of Respiratory Tract Infections During Early Childhood. (19th June 2020)

• Record Type: Journal Article
• Authors: Lempainen, Johanna; Korhonen, Laura S; Kantojärvi, Katri; Heinonen, Santtu; Toivonen, Laura; Räty, Panu; Ramilo, Octavio; Mejias, Asuncion; Laine, Antti-Pekka; Vuorinen, Tytti; Waris, Matti; Karlsson, Linnea; Karlsson, Hasse; Paunio, Tiina; Peltola, Ville
• Is Part Of: Journal of infectious diseases. Volume 223:Number 1(2021)
• Page Start: 157
• Page End: 165
• Publication Date: 2020-06-19
• Subjects: acute otitis media -- interferon pathway -- polymorphisms -- respiratory tract infections -- transcriptome; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiaa341
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: Background: Genetic heterogeneity in type I interferon (IFN)–related gene IFI44L may account for variable susceptibility to respiratory tract infections (RTIs) in children. Methods: In 2 prospective, population-based birth cohorts, the STEPS Study and the FinnBrain Birth Cohort Study, IFI44L genotypes for rs273259 and rs1333969 were determined in relation to the development of RTIs until 1 or 2 years of age, respectively. At age 3 months, whole-blood transcriptional profiles were analyzed and nasal samples were tested for respiratory viruses in a subset of children. Results: In the STEPS Study (n = 1135), IFI44L minor/minor gene variants were associated with lower rates of acute otitis media episodes (adjusted incidence rate ratio, 0.77 [95% confidence interval, .61–.96] for rs273259 and 0.74 [.55–.99] for rs1333969) and courses of antibiotics for RTIs (0.76 [.62–.95] and 0.73 [.56–.97], respectively. In the FinnBrain cohort (n = 971), IFI44L variants were associated with lower rates of RTIs and courses of antibiotics for RTIs. In respiratory virus–positive 3-month-old children, IFI44L gene variants were associated with decreased expression levels of IFI44L and several other IFN-related genes. Conclusions: Variant forms of IFI44L gene were protective against early-childhood RTIs or acute otitis media, and they attenuated IFN pathway activation by respiratory viruses. Abstract : Common IFI44L gene variants were protective against early-childhood respiratory tract infections or acute otitis media in 2 independent birth cohorts. These polymorphisms attenuated interferon pathway activation by respiratory viruses.