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

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.

Infectivity and Progression of COVID-19 Based on Selected Host Candidate Gene Variants

“…Previous studies predicted that rs12252 C allele might produce an alternate spliced transcript that encodes an aberrant truncated protein Δ21 of IFITM3 , which reduces the cellular resistance to influenza viruses by blocking early stage of viral replication (Everitt et al, 2012 ; Compton et al, 2016 ). Association of this polymorphism has been observed in Chinese population with pandemic influenza (H1N1 09pdm), seasonal influenza (H3N2 and influenza B), and avian influenza (H7N9) (Carter et al, 2018 ). In our cohort, 11.65% of the individuals carried this allele.…”

IFITM3 Clusters on Virus Containing Endosomes and Lysosomes Early in the Influenza A Infection of Human Airway Epithelial Cells

“…The relevance of the IFITM3-mediated inhibition of IAV infection received strong support when it was shown that IFITM3 polymorphisms correlated with the severity of IAV disease in human infection [42]. The relevance of the IFITM3 rs12252-C polymorphism for severe IAV infection appears to be population-dependent [43,44,45,46,47,48], and a second IFITM3 single nucleotide polymorphism, rs34481144-A, was also reported to influence the severity of IAV infection in humans [49]. However, the mechanism of the IFITM-mediated inhibition of IAV infection remains under discussion.…”

Influenza Pathogenesis: The Effect of Host Factors on Severity of Disease

“…Host genes associated with severe influenza virus in humans with severe IAV-H1H1 and IAV-H7N9 disease in some, but not all, cohorts(135)(136)(137)(138)(139)(140)(141)(142)(143)(144). rs34481144 was associated with reduced gene expression in CD8 + T cells and severe IAV disease(110).…”