Associations Between IFI44L Gene Variants and Rates of Respiratory Tract Infections During Early Childhood
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...
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Published in | The Journal of infectious diseases Vol. 223; no. 1; pp. 157 - 165 |
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Main Authors | , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
US
Oxford University Press
04.01.2021
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Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0022-1899 1537-6613 |
DOI: | 10.1093/infdis/jiaa341 |