No Major Host Genetic Risk Factor Contributed to A(H1N1)2009 Influenza Severity.

Koldo Garcia-Etxebarria,Tomàs Pumarola,Mario Rodríguez-Dominguez,Fernando González-Candelas,Angela Domínguez,Raúl Ortiz De Lejarazu,Juan Carlos Galán,Inés Quintela,Jesús Castilla,Núria Bonet,María Alma Bracho,Marc Garcia-Garcerà,Francesc Calafell,Hiroshi Nishiura

doi:10.1371/journal.pone.0135983

Abstract

While most patients affected by the influenza A(H1N1) pandemic experienced mild symptoms, a small fraction required hospitalization, often without concomitant factors that could explain such a severe course. We hypothesize that host genetic factors could contribute to aggravate the disease. To test this hypothesis, we compared the allele frequencies of 547,296 genome-wide single nucleotide polymorphisms (SNPs) between 49 severe and 107 mild confirmed influenza A cases, as well as against a general population sample of 549 individuals. When comparing severe vs. mild influenza A cases, only one SNP was close to the conventional p = 5×10−8. This SNP, rs28454025, sits in an intron of the GSK233 gene, which is involved in a neural development, but seems not to have any connections with immunological or inflammatory functions. Indirectly, a previous association reported with CD55 was replicated. Although sample sizes are low, we show that the statistical power in our design was sufficient to detect highly-penetrant, quasi-Mendelian genetic factors. Hence, and assuming that rs28454025 is likely to be a false positive, no major genetic factor was detected that could explain poor influenza A course.

Highlights

IntroductionSome of its features caused concern, such as a higher mortality risk in infants and children than in seasonal influenza epidemics, and activity peaks out of the cold season
In 2009, the influenza A(H1N1)2009 pandemic swept the globe
The goal of the present study is to explore the existence of major genetic determinants of influenza A(H1N1) severity by comparing the genotypes of a dense array of genomewide single nucleotide polymorphisms (SNPs) in 49 severe and 107 mild influenza patients from Spain, and in a general population sample of 549 individuals

Summary

Introduction

Some of its features caused concern, such as a higher mortality risk in infants and children than in seasonal influenza epidemics, and activity peaks out of the cold season. It followed a mild course in most patients, in others it was much more aggressive for unknown reasons. Two genealogy studies in Utah and Iceland clearly demonstrated familial aggregation of the risk of influenza-associated death [2]. In the 1918 influenza epidemic in Iceland [4], the 455 deaths showed no increased risk for the cases' relatives when compared to spouse's relatives. Notice that the sample in the Icelandic study was an order of magnitude smaller than the Utah sample, and its statistical power was presumably smaller

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Conclusion