Background: Altered cytokine levels have been associated with poor outcomes among COVID-19 patients. TNF-α, IL-8 and IL-10 are key cytokines in COVID-19 pathogenesis, and CXCR-2 is a major chemokine receptor involved in inflammatory response. Polymorphisms in the genes of these proteins are proposed to influence disease outcomes. In this study, we aimed to find out the association of genetic polymorphisms in TNF-α, IL-8, IL-10 and CXCR-2 genes with susceptibility to and mortality of COVID-19. Methods: The present case-control study was conducted on 230 subjects, among whom 115 were clinically diagnosed and RT-PCR-confirmed COVID-19 patients and 115 healthy control subjects. The polymorphisms in TNFα -308 G>A (rs1800629), IL-8 -251T>A (rs4073), CXCR2 +785 C>T (rs2230054) genes were detected by ARMS -PCR assay whereas for IL-10 (-1082 G>A), rs1800896 G>A allele-specific PCR assay was used and their association with COVID-19 susceptibility and mortality was estimated by multivariate analysis. The results were analyzed for risk of infection and mortality through different inheritance models. Results: Frequencies of TNF-α rs1800629 GA, AA, IL-8 rs4073 TA, AA, IL-10 (-1082 G>A), rs1800896 GA and GG, and CXCR2 rs2230054 CT genotypes were significantly higher in COVID-19 patients compared to the control group (p < 0.05). Furthermore, COVID-19 patients had a higher frequency of the polymorphic A allele of TNF-α, the A allele of IL-8, the G allele of IL-10, and the T allele of CXCR2. The risk of susceptibility to COVID-19 was significantly associated with TNF-α rs1800629 GA, GA+AA genotypes and the A allele, IL-8 rs4073 TA, AA genotypes and A allele, IL-10 rs1800872 GA and CC genotypes and C allele, and CXCR2 rs2230054 CT and CT+CC genotypes. TNF-α-GA and AA genotypes and A allele, IL-8 TA and AA genotypes and A allele and CXCR-2 CC and CT genotypes have significant associations with mortality risk in COVID-19 patients, while GA and GG genotypes of the IL-10 are shown to confer significant protection against mortality from COVID-19. Conclusion: The findings of this study provide important insights into the COVID-19 disease and susceptibility risk. The polymorphisms in TNFα -308 G>A (rs1800629), IL-8 -251T>A (rs4073), IL-10 (-1082 G>A), rs1800896 and CXCR2 +785 C>T (rs2230054) are associated with the risk of susceptibility to COVID-19 and with mortality in COVID-19 patients. Further studies with larger sample sizes are necessary to confirm our findings.

中文翻译：

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肿瘤坏死因子-α、白介素-8、白细胞介素-10 和 CXC 趋化因子受体-2 遗传变异的分子测定及其与 COVID-19 患者疾病易感性和死亡率的关系

背景：细胞因子水平的改变与 COVID-19 患者的不良预后相关。 TNF-α、IL-8和IL-10是COVID-19发病机制中的关键细胞因子，CXCR-2是参与炎症反应的主要趋化因子受体。这些蛋白质的基因多态性被认为会影响疾病的结果。在本研究中，我们旨在找出 TNF-α、IL-8、IL-10 和 CXCR-2 基因的遗传多态性与 COVID-19 易感性和死亡率的关联。方法：本病例对照研究对 230 名受试者进行，其中 115 名临床诊断且 RT-PCR 确诊的 COVID-19 患者和 115 名健康对照受试者。通过ARMS -PCR检测TNFα -308 G>A (rs1800629)、IL-8 -251T>A (rs4073)、CXCR2 +785 C>T (rs2230054)基因的多态性，而IL-10 (-1082 G >A), rs1800896 G>使用等位基因特异性 PCR 检测，并通过多变量分析估计其与 COVID-19 易感性和死亡率的关联。通过不同的遗传模型对结果进行感染和死亡风险分析。结果：与COVID-19患者相比，TNF-α rs1800629 GA、AA、IL-8 rs4073 TA、AA、IL-10 (-1082 G>A)、rs1800896 GA和GG以及CXCR2 rs2230054 CT基因型的频率显着较高与对照组相比（p < 0.05）。此外，COVID-19患者的TNF-α多态性A等位基因、IL-8的A等位基因、IL-10的G等位基因和CXCR2的T等位基因的频率较高。 COVID-19易感风险与TNF-α rs1800629 GA、GA+AA基因型和A等位基因、IL-8 rs4073 TA、AA基因型和A等位基因、IL-10 rs1800872 GA和CC基因型和C等位基因显着相关和 CXCR2 rs2230054 CT 和 CT+CC 基因型。 TNF-α-GA和AA基因型和A等位基因、IL-8 TA和AA基因型和A等位基因以及CXCR-2 CC和CT基因型与COVID-19患者的死亡风险显着相关，而IL的GA和GG基因型与死亡风险显着相关。 -10 被证明可以显着防止因 COVID-19 造成的死亡。结论：本研究的结果为了解 COVID-19 疾病和易感风险提供了重要见解。 TNFα -308 G>A (rs1800629)、IL-8 -251T>A (rs4073)、IL-10 (-1082 G>A)、rs1800896 和 CXCR2 +785 C>T (rs2230054) 中的多态性与COVID-19 患者对 COVID-19 的易感性和死亡风险。有必要进行更大样本量的进一步研究来证实我们的发现。