TNFRSF1B 和 TNF 变体与重症 COVID-19 患者可溶性肿瘤坏死因子受体水平的差异相关。
TNFRSF1B and TNF Variants Are Associated With Differences in Levels of Soluble Tumor Necrosis Factor Receptors in Patients With Severe COVID-19.
机构信息
HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico.
Translational Research Laboratory on Aging and Pulmonary Fibrosis, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City, Mexico.
出版信息
J Infect Dis. 2022 Sep 13;226(5):778-787. doi: 10.1093/infdis/jiac101.
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.
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.
背景
肿瘤坏死因子-α（TNF-α）及其受体在 2019 年冠状病毒病（COVID-19）严重程度中的表达的遗传变异的影响尚未被探索。我们评估了 TNF（rs1800629 和 rs361525）、TNFRSF1A（rs767455 和 rs1800693）和 TNFRSF1B（rs1061622 和 rs3397）变体与 COVID-19 严重程度的关联，严重 COVID-19 患者的评估指标为有创机械通气（IMV）需求以及可溶性 TNF-α、TNFR1 和 TNFR2 的血浆水平。
方法
该遗传研究包括 1353 例患者。Taqman 测定法用于评估遗传变异。ELISA 用于测定 334 例患者血浆样本中的可溶性 TNF-α、TNFR1 和 TNFR2。
结果
与 CT + CC 基因型相比，携带 TT（TNFRSF1B rs3397）的患者的 PaO2/FiO2 水平较低。根据 TNFRSF1B rs1061622、TNF rs1800629 和 rs361525 的基因型观察到 TNFR1 和 TNFR2 的血浆水平存在差异。根据研究的遗传变异，可溶性 TNF-α水平没有差异。需要 IMV 的 COVID-19 患者的可溶性 TNFR1 和 TNFR2 水平较高。
结论
TNF 和 TNFRSFB1 中的遗传变异影响可溶性 TNFR1 和 TNFR2 的血浆水平，这与 COVID-19 的严重程度有关。
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