Genetic variants associated with severe pneumonia in A/H1N1 influenza infection

Abstract

The A/H1N1 influenza strain isolated in Mexico in 2009 caused severe pulmonary illness in a small number of exposed individuals. Our objective was to determine the influence of genetic factors on their susceptibility. We carried out a case–control association study genotyping 91 patients with confirmed severe pneumonia from A/H1N1 infection and 98 exposed but asymptomatic household contacts, using the HumanCVD BeadChip (Illumina, San Diego, CA, USA). Four risk single-nucleotide polymorphisms were significantly (p<0.0001) associated with severe pneumonia: rs1801274 (Fc fragment of immunoglobulin G, low-affinity IIA, receptor (FCGR2A) gene, chromosome 1; OR 2.68, 95% CI 1.69–4.25); rs9856661 (gene unknown, chromosome 3; OR 2.62, 95% CI 1.64–4.18); rs8070740 (RPA interacting protein (RPAIN) gene, chromosome 17; OR 2.67, 95% CI 1.63–4.39); and rs3786054 (complement component 1, q subcomponent binding protein (C1QBP) gene, chromosome 17; OR 3.13, 95% CI 1.89–5.17). All SNP associations remained significant after adjustment for sex and comorbidities. The SNPs on chromosome 17 were in linkage disequilibrium. These findings revealed that gene polymorphisms located in chromosomes 1 and 17 might influence susceptibility to development of severe pneumonia in A/H1N1 infection. Two of these SNPs are mapped within genes (FCGR2A, C1QBP) involved in the handling of immune complexes and complement activation, respectively, suggesting that these genes may confer risk due to increased activation of host immunity.

Differential Susceptibilities of Human Lung Primary Cells to H1N1 Influenza Viruses

“…In fact, influenza virus infections with inbred mouse strains have demonstrated the importance of genetic factors to variation of susceptibility to influenza (39,40). Studies with family clusters of avian influenza virus H5N1 and case studies of H1N1pdm09 patients also imply that genetic factors affect susceptibility to pandemic influenza (41)(42)(43)(44)(45). Considering the distinct genetic and epigenetic background of each donor and difference between human and mouse studies, investigating the effect of genetic or epigenetic factors on influenza susceptibility in wellcontrolled human AECs, the cells most relevant to influenza, may provide unique advantage because the response in the same type of cells will not be affected by prior influenza history, vaccination, or other environmental exposure.…”

IL1RNCoding Variant Is Associated with Lower Risk of Acute Respiratory Distress Syndrome and Increased Plasma IL-1 Receptor Antagonist

“…The IBC array covers genes with higher density than most genome-wide platforms (7,23,(25)(26)(27)(28)(29). Stage II was genotyped with the Human 610-quad (Illumina), and results were filtered for the SNPs passing stage I at P , 5 3 10 24 (7,30). Calls for nongenotyped markers were imputed using MaCH and 1,000 Genomes European haplotypes from the 11/23/10 release (31,32).…”

2009 pandemic H1N1 influenza A virus strains display differential pathogenicity in C57BL/6J but not BALB/c mice

“…29 The authors postulated that these factors might potentially play a role in susceptibility to influenza in humans. Several SNPs have been identified in trials comparing safety, immunogenicity and efficacy of influenza virus vaccines in the mannose-binding lectine (MBL) 2 gene and in the TNFα and IL-10 promoter regions.…”