Pilot screening study of targeted genetic polymorphisms for association with seasonal influenza hospital admission

Tonia C. Carter, Scott J. Hebbring, Jixia Liu, Jonathan D. Mosley, Christian M. Shaffer, Lynn C. Ivacic, Sarah Kopitzke, Elisha L. Stefanski, Rob Strenn, Maria E. Sundaram, Jennifer Meece, Murray H. Brilliant, Jill M. Ferdinands, Edward A. Belongia

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Host response to influenza is highly variable, suggesting a potential role of host genetic variation. To investigate the host genetics of severe influenza in a targeted fashion, 32 single nucleotide polymorphisms (SNPs) within viral immune response genes were evaluated for association with seasonal influenza hospitalization in an adult study population with European ancestry. SNP allele and genotype frequencies were compared between hospitalized influenza patients (cases) and population controls in a case-control study that included a discovery group (26 cases and 993 controls) and two independent, validation groups (1 with 84 cases and 4076 controls; the other with 128 cases and 9187 controls). Cases and controls had similar allele frequencies for variant rs12252 in interferon-inducible transmembrane protein 3 (IFITM3) (P > 0.05), and the study did not replicate the previously reported association of rs12252 with hospitalized influenza. In the discovery group, the preliminary finding of an association with a nonsense polymorphism (rs8072510) within the schlafen family member 13 (SFLN13) gene (P = 0.0099) was not confirmed in either validation group. Neither rs12252 nor rs8072510 showed an association according to the presence of clinical risk factors for influenza complications (P > 0.05), suggesting that these factors did not modify associations between the SNPs and hospitalized influenza. No other SNPs showed a statistically significant association with hospitalized influenza. Further research is needed to identify genetic factors involved in host response to seasonal influenza infection and to assess whether rs12252, a low-frequency variant in Europeans, contributes to influenza severity in populations with European ancestry.

Original languageEnglish (US)
Pages (from-to)436-446
Number of pages11
JournalJournal of Medical Virology
Volume90
Issue number3
DOIs
StatePublished - Mar 2018

Bibliographical note

Funding Information:
Marshfield Clinic Research Institute; Centers for Disease Control and Prevention (CDC), Grant number: U18 IP000183; National Center for Advancing Translational Sciences, Grant numbers: 9U54TR000021, UL1TR000427, UL1TR000445; National Center for Research Resources, Grant number: 1UL1RR025011; National Institute of General Medical Sciences, Grant numbers: R01GM114128, RC2GM092618; National Human Genome Research Institute, Grant numbers: U01HG8701, U01HG004603; National Library of Medicine, Grant number: K22LM011938; Vanderbilt Faculty Research Scholars Fund; National Center for Immunization and Respiratory Diseases, Grant number: U18 IP000183

Funding Information:
The authors are indebted to Steven Schrodi and David McClure for performing critical roles in experimental design and analysis, and for providing comments on the manuscript. The work was supported by grants from: Grant sponsor: Marshfield Clinic Research Institute; Grant sponsor: Centers for Disease Control and Prevention (CDC), Grant number: cooperative agreement U18 IP000183; Grant Sponsor: Clinical and Translational Science Award program through grants from the National Center for Research Resources and the National Center for Advancing Translational Sciences at the National Institutes of Health (NIH), Grant numbers: 1UL1RR025011, 9U54TR000021, UL1TR000427, and UL1TR000445; Grant sponsor: National Institute of General Medical Sciences, Grant numbers: R01GM114128 and RC2GM092618; Grant sponsor: National Human Genome Research Institute; Grant numbers: U01HG8701 and U01HG004603; Grant sponsor: National Library of Medicine, Grant number: K22LM011938; Grant sponsor: Vanderbilt Faculty Research Scholars Fund. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the CDC.

Funding Information:
Maria E. Sundaram and Edward A. Belongia received research funding from MedImmune, L.L.C., a subsidiary of AstraZeneca. The other authors declare no conflicts of interest.

Publisher Copyright:
© 2017 Wiley Periodicals, Inc.

Keywords

  • IFITM3
  • host susceptibility
  • influenza
  • polymorphisms
  • virus

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