Associations Between IFI44L Gene Variants and Rates of Respiratory Tract Infections During Early Childhood - UTU Research Portal

A1 Refereed original research article in a scientific journal

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

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

Publisher: Oxford Academic

Publication year: 2021

Journal: Journal of Infectious Diseases

Journal name in source: The Journal of infectious diseases

Journal acronym: J Infect Dis

Volume: 223

Issue: 1

First page : 157

Last page: 165

Number of pages: 9

ISSN: 0022-1899

eISSN: 1537-6613

DOI: https://doi.org/10.1093/infdis/jiaa341

Web address : https://academic.oup.com/jid/article/223/1/157/5860160

Self-archived copy’s web address: https://helda.helsinki.fi/handle/10138/331643

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.