A systematic review and meta-analysis of host genetic factors associated with influenza severity

Nina Van Goethem,Nathalie Bossuyt,Herman Van Oyen,Nancy H C Roosens,Célestin Danwang,Annie Robert

doi:10.1186/s12864-021-08240-7

Abstract

BackgroundThe severity of influenza disease can range from mild symptoms to severe respiratory failure and can partly be explained by host genetic factors that predisposes the host to severe influenza. Here, we aimed to summarize the current state of evidence that host genetic variants play a role in the susceptibility to severe influenza infection by conducting a systematic review and performing a meta-analysis for all markers with at least three or more data entries.ResultsA total of 34 primary human genetic association studies were identified that investigated a total of 20 different genes. The only significant pooled ORs were retrieved for the rs12252 polymorphism: an overall OR of 1.52 (95% CI [1.06–2.17]) for the rs12252-C allele compared to the rs12252-T allele. A stratified analysis by ethnicity revealed opposite effects in different populations.ConclusionWith exception for the rs12252 polymorphism, we could not identify specific genetic polymorphisms to be associated with severe influenza infection in a pooled meta-analysis. This advocates for the use of large, hypothesis-free, genome-wide association studies that account for the polygenic nature and the interactions with other host, pathogen and environmental factors.

Highlights

The severity of disease resulting from infection with influenza viruses can range from mild symptoms to severe respiratory failure
There was a total of four genetic polymorphisms that had at least three data entries and for which a meta-analysis was conducted
The included primary human genetic association studies, conducted within influenza positive patient cohorts, investigated whether patients with increased susceptibility to severe influenza disease had impaired intracellular control of viral replication (e.g. interferon-induced transmembrane protein 3 (IFITM3) [27,28,29,30,31,32,33,34,35,36,37], Transmembrane serine protease 2 (TMPRSS2) [38] variants), defective interferon responses (e.g. Glycine decarboxylase (GLDC) [39] variants), polymorphisms in genes implicated in the cytokine response (e.g. Tumor necrosis factor (TNF) [40], C-C motif chemokine receptor 5 (CCR5) [41,42,43,44] variants), dysfunction of proteins related to the

Summary

Introduction

The severity of disease resulting from infection with influenza viruses can range from mild symptoms to severe respiratory failure. This variability is due to multiple host- and pathogen-related factors and the interplay between them. The World Health Organization (WHO) prioritizes the identification of host genetic factors that predispose the host to severe influenza [23]. This leads to a better understanding of the biological mechanisms behind the development of severe disease, which may reveal new therapeutic approaches and may enable effective targets for vaccine therapies. We aimed to summarize the current state of evidence that host genetic variants play a role in the susceptibility to severe influenza infection by conducting a systematic review and performing a meta-analysis for all markers with at least three or more data entries

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Conclusion