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J Infect Dis. 2017 Jul 1;216(1):14-21. doi: 10.1093/infdis/jix242.

Evaluation of IFITM3 rs12252 Association With Severe Pediatric Influenza Infection.

Author information

1
Department of Anesthesia, Perioperative and Pain Medicine, Boston Children's Hospital.
2
Departments of Anaesthesia and Pediatrics, Harvard Medical School, Boston.
3
Foundation Medicine Inc, Cambridge, Massachusetts.
4
Department of Immunology, St Jude Children's Research Hospital, Memphis, Tennessee.
5
Biomarker Discovery, Genentech, Inc, South San Francisco, California.
6
Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
7
Human Genetics, Genentech, Inc, South San Francisco, California.
8
Department of Computational Biology, St Jude Children's Research Hospital, Memphis, Tennessee.
9
Pediatric Critical Care, UCSF Benioff Children's Hospital Oakland, California.
10
Section of Critical Care, Department of Pediatrics, University of Colorado School of Medicine and Research Institute, Children's Hospital Colorado, Aurora.
11
Critical Care Medicine, Nationwide Children's Hospital, Columbus, Ohio.

Abstract

Background:

Interferon-induced transmembrane protein 3 (IFITM3) restricts endocytic fusion of influenza virus. IFITM3 rs12252_C, a putative alternate splice site, has been associated with influenza severity in adults. IFITM3 has not been evaluated in pediatric influenza.

Methods:

The Pediatric Influenza (PICFLU) study enrolled children with suspected influenza infection across 38 pediatric intensive care units during November 2008 to April 2016. IFITM3 was sequenced in patients and parents were genotyped for specific variants for family-based association testing. rs12252 was genotyped in 54 African-American pediatric outpatients with influenza (FLU09), included in the population-based comparisons with 1000 genomes. Splice site analysis of rs12252_C was performed using PICFLU and FLU09 patient RNA.

Results:

In PICFLU, 358 children had influenza infection. We identified 22 rs12252_C homozygotes in 185 white non-Hispanic children. rs12252_C was not associated with influenza infection in population or family-based analyses. We did not identify the Δ21 IFITM3 isoform in RNAseq data. The rs12252 genotype was not associated with IFITM3 expression levels, nor with critical illness severity. No novel rare IFITM3 functional variants were identified.

Conclusions:

rs12252 was not associated with susceptibility to influenza-related critical illness in children or with critical illness severity. Our data also do not support it being a splice site.

KEYWORDS:

IFITM3; genetic susceptibility; influenza; interferon-inducible transmembrane protein; pediatric

PMID:
28531322
PMCID:
PMC5853450
DOI:
10.1093/infdis/jix242
[Indexed for MEDLINE]
Free PMC Article

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