| Title | Associations Between IFI44L Gene Variants and Rates of Respiratory Tract Infections During Early Childhood. | ||
| Author | Lempainen, Johanna; Korhonen, Laura S; Kantojarvi, Katri; Heinonen, Santtu; Toivonen, Laura; Raty, Panu; Ramilo, Octavio; Mejias, Asuncion; Laine, Antti-Pekka; Vuorinen, Tytti; Waris, Matti; Karlsson, Linnea; Karlsson, Hasse; Paunio, Tiina; Peltola, Ville | ||
| Journal | J Infect Dis | Publication Year/Month | 2021-Jan |
| PMID | 32561935 | PMCID | -N/A- |
| Affiliation + expend | 1.Department of Paediatrics and Adolescent Medicine, University of Turku and Turku University Hospital, Turku, Finland. | ||
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.