Association of Tumor Necrosis Factor-Alpha (TNF-α) and Suppressor of Cytokine Signaling-1 (SOCS-1) Gene Variants in Children with COVID-19

Abstract

Objective The suppressor of cytokine signaling-1 (SOCS-1) gene is an essential physiological regulator of cytokine signaling. Tumor necrosis factor-α (TNF-α) is an important component of the immunological response. Herein, we aimed to investigate the effects of SOCS-1 (-1478 CA > Del) and TNF-α (-308) polymorphisms on disease susceptibility and prognosis in pediatric patients with coronavirus disease 2019 (COVID-19).

Methods One-hundred fifty COVID-19 patients in the COVID-19 emergency department between September 2020 and April 2021 and 80 healthy volunteers (control group) without any additional disease were included. Baseline gene polymorphisms were compared between the patient and healthy control groups. Afterward, the gene polymorphism distribution was examined by forming two separate clinical patients' subgroups.

Results While CA/CA and CA/Del gene variants of SOCS-1 were higher in the patient group, Del/Del genotype was more common in the control group (p < 0.05). The GG genotype of the TNF-α was significantly more common in the severe subgroup (p = 0.044). The GA genotype of TNF-α was associated with the risk of hospitalization (2.83-fold), while the GG genotype was found to be protective in terms of hospitalization (2.95-fold).

Conclusions This study will be a guide in terms of the presence of high cytokine release genotypes and COVID-19-related cytokine release syndromes.

Keywords

COVID-19 - SOCS-1 - TNF-α - cytokines

• References

• 1 Zhou P, Yang XL, Wang XG. et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020; 579 (7798): 270-273
• 2 Abrams EM, Greenhawt M. Risk communication during COVID-19. J Allergy Clin Immunol Pract 2020; 8 (06) 1791-1794
• 3 Guedes RA, Planello AC, Andia DC, De Oliveira NF, de Souza AP. Association of SOCS1 (- 820) (rs33977706) gene polymorphism with chronic periodontitis: a case-control study in Brazilians. Meta Gene 2015; 5: 124-128
• 4 Harada M, Nakashima K, Hirota T. et al. Functional polymorphism in the suppressor of cytokine signaling 1 gene associated with adult asthma. Am J Respir Cell Mol Biol 2007; 36 (04) 491-496
• 5 Brand S, Zitzmann K, Dambacher J. et al. SOCS-1 inhibits expression of the antiviral proteins 2′,5′-OAS and MxA induced by the novel interferon-lambdas IL-28A and IL-29. Biochem Biophys Res Commun 2005; 331 (02) 543-548
• 6 Brinkman BM, Zuijdeest D, Kaijzel EL, Breedveld FC, Verweij CL. Relevance of the tumor necrosis factor alpha (TNF alpha) -308 promoter polymorphism in TNF alpha gene regulation. J Inflamm 1995-1996; 46 (01) 32-41
• 7 Kroeger KM, Steer JH, Joyce DA, Abraham LJ. Effects of stimulus and cell type on the expression of the -308 tumour necrosis factor promoter polymorphism. Cytokine 2000; 12 (02) 110-119
• 8 Rokni M, Ghasemi V, Tavakoli Z. Immune responses and pathogenesis of SARS-CoV-2 during an outbreak in Iran: comparison with SARS and MERS. Rev Med Virol 2020; 30 (03) e2107
• 9 Wilson AG, di Giovine FS, Blakemore AI, Duff GW. Single base polymorphism in the human tumour necrosis factor alpha (TNF alpha) gene detectable by NcoI restriction of PCR product. Hum Mol Genet 1992; 1 (05) 353
• 10 Oz Gul O, Cander S, Gul CB, Budak F, Oral B, Ersoy C. Cytokine signal suppressor (SOCS) 1-1478 CA/del gene polymorphism in Turkish patients with polycystic ovary syndrome. J Obstet Gynaecol 2017; 37 (07) 896-901
• 11 Akcali A, Pehlivan S, Pehlivan M, Sever T, Akgul P, Neyal M. TNF-alpha promoter polymorphisms in multiple sclerosis: no association with -308 and -238 alleles, but the -857 alleles in associated with the disease in Turkish patients. Int J Immunogenet 2010; 37 (02) 91-95
• 12 Akhtar LN, Benveniste EN. Viral exploitation of host SOCS protein functions. J Virol 2011; 85 (05) 1912-1921
• 13 Sun K, Salmon S, Yajjala VK, Bauer C, Metzger DW. Expression of suppressor of cytokine signaling 1 (SOCS1) impairs viral clearance and exacerbates lung injury during influenza infection. PLoS Pathog 2014; 10 (12) e1004560
• 14 Santiago AM, da Silva Graça Amoras E, Queiroz MAF. et al. TNFA -308G>A and IL10 -1082A>G polymorphisms seem to be predictive biomarkers of chronic HCV infection. BMC Infect Dis 2021; 21 (01) 1133
• 15 Mahdinejad-Yazdi M, Sobhan MR, Dastgheib SA. et al. A meta-analysis for association of TNF-α -308G>A polymorphism with susceptibility to ankylosing spondylitis. J Orthop 2021; 26: 79-87
• 16 Shi LX, Zhang L, Zhang DL. et al. Association between TNF-α G-308A (rs1800629) polymorphism and susceptibility to chronic periodontitis and type 2 diabetes mellitus: a meta-analysis. J Periodontal Res 2021; 56 (02) 226-235
• 17 Zhang X, Zhu X, Sun W. Association between tumor necrosis factor-α (G-308A) polymorphism and chronic periodontitis, aggressive periodontitis, and peri-implantitis: a meta-analysis. J Evid Based Dent Pract 2021; 21 (03) 101528
• 18 Saleh A, Sultan A, Elashry MA. et al. Association of TNF-α G-308 a promoter polymorphism with the course and outcome of COVID-19 patients. Immunol Invest 2022; 51 (03) 546-557
• 19 Rokni M, Sarhadi M, Heidari Nia M. et al. Single nucleotide polymorphisms located in TNFA, IL1RN, IL6R, and IL6 genes are associated with COVID-19 risk and severity in an Iranian population. Cell Biol Int 2022; 46 (07) 1109-1127
• 20 Heidari Nia M, Rokni M, Mirinejad S. et al. Association of polymorphisms in tumor necrosis factors with SARS-CoV-2 infection and mortality rate: a case-control study and in silico analyses. J Med Virol 2022; 94 (04) 1502-1512
• 21 Khan S, Mandal RK, Jawed A. et al. TNF-α -308 G > A (rs1800629) polymorphism is associated with celiac disease: a meta-analysis of 11 case-control studies. Sci Rep 2016; 6: 32677