Associations Between IFI44L Gene Variants and Rates of Respiratory Tract Infections During Early Childhood

• Published in: The Journal of infectious diseases Vol. 223; no. 1; pp. 157 - 165
• Main 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
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 04.01.2021
• Subjects: Antibiotics; Children; Ear diseases; Genotypes; Interferon; Otitis media; Respiratory tract diseases; Respiratory tract infection; Transcription; acute otitis media; respiratory tract infections; interferon pathway; polymorphisms; transcriptome
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiaa341

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. 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.