Association of polymorphisms in inflammatory cytokines encoding genes with severe cases of influenza A/H1N1 and B in an

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RESEARCH

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Association of polymorphisms in inflammatory cytokines encoding genes with severe cases of influenza A/H1N1 and B in an Iranian population Mohsen Keshavarz1,2, Haideh Namdari3, Mohammad Farahmand4, Parvaneh Mehrbod5, Talat Mokhtari-Azad4 and Farhad Rezaei4*

Abstract Background: The increased levels of blood cytokines is the main immunopathological process that were attributed to severe clinical outcomes in cases of influenza A, influenza B and people with influenza-like illness (ILI). Functional genetic polymorphisms caused by single nucleotide polymorphisms (SNPs) in inflammatory cytokines genes can influence their functions either qualitatively or quantitatively, which is associated with the possibility of severe influenza infections. The aim of the present case-control study was to investigate the association of polymorphisms in inflammatory cytokines genes with influenza patients and ILI group in an Iranian population. Methods: Total number of 30 influenza B, 50 influenza A (H1N1) and 96 ILI inpatient individuals were confirmed by Real-time RT-PCR and HI assays. The genotype determination was assessed for defined SNPs in IL-1β, IL-17, IL-10 and IL-28 genes. Results: The frequencies of the IL-1β rs16944 (P = 0.007) and IL-17 rs2275913 (P = 0.006) genotypes were associated with severe influenza disease, while the frequencies of IL-10 rs1800872 and IL-28 rs8099917 were not associated with the disease (P > 0.05). Also, the absence of A allele in IL-17 rs2275913 SNP increased the risk of influenza A (H1N1) infection (P = 0.008). Conclusions: This study demonstrated that influenza A- (H1N1) and B-infected patients and also ILI controls have different profiles of immune parameters, and individuals carrying the specific cytokine-derived polymorphisms may show different immune responses towards severe outcome. Keywords: Influenza, Cytokine, Inflammatory response, Single nucleotide polymorphism, Influenza-like illness

Background Influenza viruses are known as worldwide human and livestock pathogens which have caused serious respiratory diseases and deaths over the past century [1–3]. Influenza viruses have always had potential to cause widespread pandemics whenever several risk factors including live poultry market, climatic factors and most importantly susceptibility of type A to high diversity upon combination of different pathogenic hemagglutinins (HA) * Correspondence: [email protected] 4 Department of Virology, School of Public Health, National Influenza Center, Tehran University of Medical Sciences, Tehran, Iran Full list of author information is available at the end of the article

and neuraminidases (NA) proteins are available [4, 5]. Since H1N1 has been known as responsible for 2009 pandemic, upon evaluation of the 3672 confirmed cases of influenza A (H1N1) in Iran between 22 May and 21 December 2009, Gouya and colleagues reported that infections occurred in all age groups with and without any predisposing factors [6]. Further, according to the data obtained from www.who.int/flunet, and