Abstract:
Tumor necrosis factor (TNF) and interferon-gamma (IFNγ) are important inflammatory mediators in the development of cytokine storm syndrome (CSS). Single nucleotide polymorphisms (SNPs) regulate the expression of these cytokines, making host genetics a key factor in the prognosis of COVID-19. In this study, we investigated the associations of the TNF -308G/A and IFNG +874T/A polymorphisms with COVID-19. We analyzed the frequencies of the two polymorphisms in the control groups (CG: TNF -308G/A, n = 497; IFNG +874T/A, n = 397), a group of patients with COVID-19 (CoV, n = 222) and among the subgroups of patients with nonsevere (n = 150) and severe (n = 72) COVID-19. We found no significant difference between the genotypic and allelic frequencies of TNF -308G/A in the groups analyzed; however, both the frequencies of the high expression genotype (TT) (CoV: 13.51% vs. CG: 6.30%; p = 0.003) and the *T allele (CoV: 33.56% vs. CG: 24. 81%; p = 0.001) of the IFNG +874T/A polymorphism were higher in the COVID-19 group than in the control group, with no differences between the subgroups of patients with nonsevere and severe COVID-19. The *T allele of IFNG +874T/A (rs2430561) is associated with susceptibility to symptomatic COVID-19. These SNPs provided valuables clues about the potential mechanism involved in the susceptibility to developing symptomatic COVID-19.
摘要:
肿瘤坏死因子(TNF)和干扰素-γ(IFNγ)是细胞因子风暴综合征(CSS)发展中的重要炎症介质。单核苷酸多态性(SNPs)调节这些细胞因子的表达,使宿主遗传学成为COVID-19预后的关键因素。在这项研究中,我们调查了TNF-308G/A和IFNG+874T/A多态性与COVID-19的相关性。我们分析了对照组中两种多态性的频率(CG:TNF-308G/A,n=497;IFNG+874T/A,n=397),一组COVID-19患者(CoV,n=222),在非重症(n=150)和重症(n=72)COVID-19患者的亚组中。我们发现在所分析的组中,TNF-308G/A的基因型和等位基因频率之间没有显著差异;然而,高表达基因型(TT)的频率均为(CoV:13.51%vs.CG:6.30%;p=0.003)和*T等位基因(CoV:33.56%vs.CG:24.81%;p=0.001)IFNG+874T/A多态性在COVID-19组中高于对照组,非重度和重度COVID-19患者亚组之间没有差异。IFNG+874T/A(rs2430561)的*T等位基因与有症状的COVID-19的易感性相关。这些SNP提供了有关发展有症状的COVID-19易感性的潜在机制的有价值的线索。