Abstract

Background Single Nucleotide Polymorphisms (SNPs) in genes influencing hypercytokinemia have been implicated in the clinical manifestations of severe influenza infection. Genotype-phenotype studies in healthy subjects may help to identify biomarkers of early prediction for severe disease outcome. Objective The aim of this study was to determine the association between genetic risk factors of severe influenza infection related to SNPs in hypercytokinemia genes and the plasma proteome markers in Canadian healthy young adults. Methods Subjects were from the Toronto Nutrigenomics and Health Study and included Caucasian men and women (n = 433) who completed a general health and lifestyle questionnaire and provided a fasting blood sample. Polymorphisms in the TNF (rs1800629), CCL1 (rs2282691), IL8 (rs4073) and LTα (rs909253) genes were extracted from an Affymetrix 6.0 chip and 54 plasma proteins were assayed by a mass spectrometry-based multiple reaction monitoring method. Results The frequency of risk genotypes of rs2282691 (AA), rs4073 (TA), rs909253 (AG) and rs1800629 (GA) were, 42%, 44%, 40% and 24%, respectively. Participants were separated into four risk subgroups (zero-, one-, two- and ≥ three-risk genotypes) based on the number of risk genotypes of the four examined SNPs. Eighteen proteomic markers were significantly correlated with the number of risk genotypes. Several of these proteins were involved in the innate immune pathway such as haptoglobin-β chain (r = 0.34, p = 0.039), complement factor B (r = 0.32, p = 0.05), complement C9 (r = 0.31, p = 0.049) and downstream acute phase reactants such as CRP (r = 0.33, p = 0.043) and hemopexin (r = 0.34, p = 0.039). Conclusion Polymorphisms in genes related to hypercytokinemia and risk of severe influenza infection are associated with a proteomics profile linked to biomarkers involved in the innate immune system. This outcome may permit identifying public health measures for early risk prediction and prevention of severe outcome upon infection with influenza virus.

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