TNFA and IL10 Polymorphisms and IL-6 and IL-10 Levels Influence Disease Severity in Influenza A(H1N1)pdm09 Virus Infected Patients

• Published in: Genes Vol. 12; no. 12; p. 1914
• Main Authors: Alagarasu, Kalichamy, Kaushal, Himanshu, Shinde, Pooja, Kakade, Mahadeo, Chaudhary, Urmila, Padbidri, Vikram, Sangle, Shashikala A., Salvi, Sonali, Bavdekar, Ashish R., D’costa, Pradeep, Choudhary, Manohar Lal
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28.11.2021; MDPI
• Subjects: Adult; Alleles; biomarkers; Biomarkers - metabolism; Cytokines; death; disease severity; Female; Genotype & phenotype; Haplotypes; Humans; Immune response; Infections; Inflammation; influenza; Influenza A; Influenza A Virus, H1N1 Subtype - genetics; Influenza A Virus, H1N1 Subtype - immunology; Influenza A Virus, H1N1 Subtype - isolation & purification; Influenza, Human - genetics; Influenza, Human - immunology; Influenza, Human - pathology; Influenza, Human - virology; Interleukin 1; Interleukin 10; Interleukin 17; Interleukin 2; Interleukin 4; Interleukin 6; Interleukin-10 - blood; Interleukin-10 - genetics; Interleukin-6 - blood; Male; Middle Aged; pathogenesis; Patients; Plasma; Polymorphism, Single Nucleotide; Severity of Illness Index; Single-nucleotide polymorphism; Swine flu; Tumor necrosis factor; Tumor Necrosis Factor-alpha - blood; Tumor Necrosis Factor-alpha - genetics; Tumor necrosis factor-TNF; Ventilators; Viruses; γ-Interferon; United States > US; India; cytokines; TNF-α; gene polymorphisms; influenza A(H1N1)pdm09; interleukins
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes12121914

Cytokines are key modulators of immune response, and dysregulated production of proinflammatory and anti-inflammatory cytokines contributes to the pathogenesis of influenza A(H1N1)pdm09 virus infection. Cytokine production is impacted by single nucleotide polymorphisms (SNPs) in the genes coding for them. In the present study, SNPs in the IL6, TNFA, IFNG, IL17A, IL10, and TGFB were investigated for their association with disease severity and fatality in influenza A(H1N1)pdm09-affected patients with mild disease (n = 293) and severe disease (n = 86). Among those with severe disease, 41 patients had fatal outcomes. In a subset of the patients, levels of IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, and IL-17 were assayed in the plasma for their association with severe disease. The frequency of TNFA rs1800629 G/A allele was significantly higher in severe cases and survived severe cases group compared to that of those with mild infection (OR with 95% for mild vs. severe cases 2.95 (1.52–5.73); mild vs. survived severe cases 4.02 (1.84–8.82)). IL10 rs1800896-rs1800872 G-C haplotype was significantly lower (OR with 95% 0.34 (0.12–0.95)), while IL10 rs1800896-rs1800872 G-A haplotype was significantly higher (OR with 95% 12.11 (2.23–76.96)) in fatal cases group compared to that of the mild group. IL-6 and IL-10 levels were significantly higher in fatal cases compared to that of survived severe cases. IL-6 levels had greater discriminatory power than IL-10 to predict progression to fatal outcome in influenza A(H1N1)pdm09 virus-infected patients. To conclude, the present study reports the association of TNFA and IL10 SNPs with severe disease in Influenza A(H1N1)pdm09 virus-infected subjects. Furthermore, IL-6 levels can be a potential biomarker for predicting fatal outcomes in Influenza A(H1N1)pdm09 virus infected subjects.