Faculty Collaboration Database

Evaluation of IFITM3 rs12252 Association With Severe Pediatric Influenza Infection. J Infect Dis 2017 Jul 01;216(1):14-21

Date

05/23/2017

Pubmed ID

28531322

Pubmed Central ID

PMC5853450

DOI

10.1093/infdis/jix242

Scopus ID

2-s2.0-85024473634 (requires institutional sign-in at Scopus site)   44 Citations

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.

Author List

Randolph AG, Yip WK, Allen EK, Rosenberger CM, Agan AA, Ash SA, Zhang Y, Bhangale TR, Finkelstein D, Cvijanovich NZ, Mourani PM, Hall MW, Su HC, Thomas PG, Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Pediatric Influenza (PICFLU) Investigators, Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Pediatric Influenza (PICFLU) Investigators

Author

Rainer G. Gedeit MD Associate Chief Medical Officer in the Children's Administration department at Children's Wisconsin

MESH terms used to index this publication - Major topics in bold

Child
Child, Preschool
Female
Genetic Predisposition to Disease
Genotyping Techniques
Homozygote
Humans
Influenza A virus
Influenza, Human
Male
Membrane Proteins
Polymorphism, Single Nucleotide
Prospective Studies
Protein Isoforms
RNA, Viral
RNA-Binding Proteins