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

J Med Virol. 2018 Mar;90(3):436-446. doi: 10.1002/jmv.24975. Epub 2017 Nov 11.


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.

Keywords: IFITM3; host susceptibility; influenza; polymorphisms; virus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Electronic Health Records
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genetic Testing*
  • Genetic Variation
  • Genotype
  • Hospitalization / statistics & numerical data*
  • Humans
  • Influenza A Virus, H1N1 Subtype
  • Influenza, Human / genetics*
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Pilot Projects
  • Polymorphism, Single Nucleotide
  • RNA-Binding Proteins / genetics


  • IFITM3 protein, human
  • Membrane Proteins
  • RNA-Binding Proteins