Torres-Poveda Kirvis, Bahena-Román Margarita, Contreras-Ochoa Carla O, Lagunas-Martínez Alfredo, Bermúdez-Morales Víctor Hugo, Pando-Robles Victoria, Ortiz-Flores Esmeralda, Cortés-Pedroza Fabiola, Santana-Román María E, Martínez-Campos Cecilia, Sánchez-Alemán Miguel, Manzo-Merino Joaquin, Morales-Ortega Ausencio, Madrid-González Daniel Alberto, Cantú-Cuevas Marco Antonio, Barón-Olivares Héctor, Madrid-Marina Vicente
Center for Research on Infectious Diseases, Instituto Nacional de Salud Pública (INSP), Cuernavaca, Mexico.
Secretaria de Ciencia, Humanidades, Tecnología e Innovación (SECIHTI)-Instituto Nacional de Salud Pública, Cuernavaca, Mexico.
BMC Infect Dis. 2025 Mar 5;25(1):315. doi: 10.1186/s12879-025-10695-y.
COVID-19 was the leading cause of death in Mexico between 2020 and 2021. SARS-CoV-2 infection varies widely among individuals and populations. Since variations in genes related to the immune response may play a role in the susceptibility to and outcome of COVID-19, the associations of gene polymorphisms (SNPs) of IL-6 (- 573G > C, rs1800796), TNF-α (- 308G > A, rs1800629), and IFN-γ (- 1615 C > T, rs2069705) with the expression levels of these proteins in the nasopharynx and serum were evaluated in a Mexican population with mild, severe, or critical COVID-19.
A total of 560 COVID-19 patients (309 mild, 163 severe, and 88 critical cases) and 560 age- and sex-matched COVID-19-negative controls were recruited for this case‒control study. The selected SNPs were genotyped via allelic discrimination. Logistic regression analysis was conducted considering four models of inheritance, and ORs were determined for each genotypic variant, adjusting for associated comorbidities in the multivariate model. The nasopharyngeal mRNA expression levels of IL-6, IFN-γ and TNF-α were determined. The levels of IL-6, IFN-γ, IFN-α2, and TNF-α in the serum were quantified. Significant differences were assessed via the Wilcoxon Mann‒Whitney U test.
The C allele of the IL-6 - 573 SNP was associated with a greater risk of mild and severe COVID-19 (OR: 2.3, CI: 1.897-2.838, p = 0.0001; and OR: 1.5, CI: 1.167-1.949, p = 0.002, respectively), whereas the A allele of the TNF-α - 308 SNP and the T allele of the IFN-γ - 1615 SNP were shown protective roles against severe COVID-19 (OR: 0.3, CI: 0.189-0.537, p = 0.0001; and OR: 0.7, CI: 0.563-1.006, p = 0.05) and against critical COVID-19 (OR: 0.3, CI: 0.158-0.640, p = 0.001; and OR: 0.4, CI: 0.290-0.678, p = 0.0001), adjusting for diabetes and hypertension. Nasopharyngeal IL-6 expression levels were lower in mild COVID-19 patients (p = 0.001) than in critical patients (p = 0.005). Serum IL-6 levels were significantly elevated in the critical cases (p = 0.01).
Our results revealed that the IL-6 - 573 G > C SNP and increased IL-6 nasopharyngeal and serum levels are associated with the risk of severe COVID-19 in a Mexican population.
2020年至2021年期间，新型冠状病毒肺炎（COVID-19）是墨西哥的主要死因。严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染在个体和人群中差异很大。由于与免疫反应相关的基因变异可能在COVID-19的易感性和结局中起作用，因此在患有轻度、重度或危重型COVID-19的墨西哥人群中，评估了白细胞介素-6（IL-6，-573G＞C，rs1800796）、肿瘤坏死因子-α（TNF-α，-308G＞A，rs1800629）和干扰素-γ（IFN-γ，-1615C＞T，rs2069705）基因多态性（单核苷酸多态性，SNPs）与这些蛋白在鼻咽和血清中的表达水平之间的关联。
本病例对照研究共纳入560例COVID-19患者（309例轻度、163例重度和88例危重型）和560例年龄和性别匹配的COVID-19阴性对照。通过等位基因鉴别对选定的SNPs进行基因分型。考虑四种遗传模型进行逻辑回归分析，并确定每个基因型变异的比值比（OR），在多变量模型中对相关合并症进行校正。测定IL-6、IFN-γ和TNF-α的鼻咽mRNA表达水平。定量血清中IL-6、IFN-γ、IFN-α2和TNF-α的水平。通过Wilcoxon Mann-Whitney U检验评估显著差异。
校正糖尿病和高血压后，IL-6 - 573 SNP的C等位基因与轻度和重度COVID-19的较高风险相关（OR分别为：2.3，CI：1.897-2.838，p = 0.0001；以及OR：1.5，CI：1.167-1.949，p = 0.002），而TNF-α - 308 SNP的A等位基因和IFN-γ - 1615 SNP的T等位基因对重度COVID-19（OR：0.3，CI：0.189-0.537，p = 0.0001；以及OR：0.7，CI：0.563-1.006，p = 0.05）和危重型COVID-19（OR：0.3，CI：0.158-0.640，p = 0.001；以及OR：0.4，CI：0.290-0.678，p = 0.0001）显示出保护作用。轻度COVID-19患者的鼻咽IL-6表达水平低于危重型患者（p = 0.001）（p = 0.005）。危重型病例的血清IL-6水平显著升高（p = 0.01）。
我们的结果显示，在墨西哥人群中，IL-6 - 573 G＞C SNP以及鼻咽和血清中IL-6水平升高与重度COVID-19风险相关。
