TNFRSF1B and TNF Variants Are Associated With Differences in Levels of Soluble Tumor Necrosis Factor Receptors in Patients With Severe COVID-19

TNFRSF1B 和 TNF 变异与重症 COVID-19 患者可溶性肿瘤坏死因子受体水平差异有关

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作者:Ingrid Fricke-Galindo, Ivette Buendía-Roldán, Andy Ruiz, Yadira Palacios, Gloria Pérez-Rubio, Rafael de Jesus Hernández-Zenteno, Felipe Reyes-Melendres, Armando Zazueta-Márquez, Aimé Alarcón-Dionet, Javier Guzmán-Vargas, Omar Andrés Bravo-Gutiérrez, Teresa Quintero-Puerta, Ilse Adriana Gutiérrez-Pér

Background

The impact of genetic variants in the expression of tumor necrosis factor-α (TNF-α) and its receptors in coronavirus disease 2019 (COVID-19) severity has not been previously explored. We evaluated the association of TNF (rs1800629 and rs361525), TNFRSF1A (rs767455 and rs1800693), and TNFRSF1B (rs1061622 and rs3397) variants with COVID-19 severity, assessed as invasive mechanical ventilation (IMV) requirement, and the plasma levels of soluble TNF-α, TNFR1, and TNFR2 in patients with severe COVID-19.

Conclusions

Genetic variants in TNF and TNFRSFB1 influence the plasma levels of soluble TNFR1 and TNFR2, implicated in COVID-19 severity.

Methods

The genetic study included 1353 patients. Taqman assays were used to assess the genetic variants. ELISA was used to determine soluble TNF-α, TNFR1, and TNFR2 in plasma samples from 334 patients.

Results

Patients carrying TT (TNFRSF1B rs3397) exhibited lower PaO2/FiO2 levels than those with CT + CC genotypes. Differences in plasma levels of TNFR1 and TNFR2 were observed according to the genotype of TNFRSF1B rs1061622, TNF rs1800629, and rs361525. According to the studied genetic variants, there were no differences in the soluble TNF-α levels. Higher soluble TNFR1 and TNFR2 levels were detected in patients with COVID-19 requiring IMV. Conclusions: Genetic variants in TNF and TNFRSFB1 influence the plasma levels of soluble TNFR1 and TNFR2, implicated in COVID-19 severity.

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