The role of tumor necrosis factor alpha − 308A > G polymorphism on the clinical states of SARS-CoV-2 infection

Abstract

Background Tumor necrosis factor-alpha (TNFɑ) is a cytokine that manages the host defense mechanism, which may play a role in the pathogenesis of COVID-19 patients. Several single-nucleotide polymorphisms, described in the promoter region of the TNFα gene, have a significant role on its transcriptional activity. These include the − 308A > G polymorphism which increases the TNFα levels with the expression of the A allele. The aim of this study was to explore whether the TNFα.− 308A > G polymorphism affects the clinical state of COVID-19 patients. The study included a total of 1028 individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which were distributed in 3 groups: asymptomatic, mild symptomatic and severe symptomatic patients. The amplification-refractory mutation system was used to determine the genotype of the TNFα.− 308A > G polymorphism. Results Results show a higher tendency of being asymptomatic in individuals carrying the GG genotype (336 of 411; OR 1.24, 95% CI 0.91–1.70). The development of a severe form of SARS-CoV-2 infection was not found in subjects with the A allele compared to those with the G allele (OR 0.96, 95% CI 0.51–1.79), except in the eastern region of the country where the risk increased (OR 4.41, 95% CI 1.14–17.05). However, the subjects carrying the A allele had a higher chance of developing symptoms (OR 1.24, 95% CI 0.91–1.70) compared to those with the G allele. Conclusion The TNFα.− 308A allele has an influence on developing symptoms of COVID-19 in Cuban patients, and that it particularly increases the risk of presenting severe forms of the disease in the eastern region of the country.

Frequency of Interleukin-6 rs 1800796 (-572G/C) and 2069837 (intron 2A/G), TNF-α rs1800750 (-376G/A), and 1800629 (-308G/A) polymorphism in COVID-19 patients with clinical degrees in Central Java

“…The low frequency of the A allele and TNF-α (-376G/A) AA Polymorphism in this population may be due to natural selection preferring individuals with low production potential to individuals with high TNFα secretion, so that the A allele is rare in cases of SARS CoV2 infection. 5 Different results were reported by Saleh A et al, 2020 that people carrying the A allele (AA and AG) are more susceptible to SARS CoV2 infection, even in the study it was stated that the AA genotype was associated with a more aggressive disease and a less favorable disease course compared to other genotypes. 4 The reason for this difference is probably because we did not control for allele and genotype frequencies according to ethnic background.…”

“…4 The reason for this difference is probably because we did not control for allele and genotype frequencies according to ethnic background. 5 The IL-6 (-572G/C) polymorphism for cases requiring medium and severe clinical degree hospitalization was found to have more C allele than G allele. The same thing also happened to IL-6 (intron A/G) for cases requiring hospitalization, the allele A is more abundant than the G allele.…”

“…4 TNF-α and IL-6 have potent pro-inflammatory actions, exerting a pleiotropic effect on various cell types. 4,5 Polymorphism studies for SARS CoV2 in Indonesia is still rare. This evaluation is aimed at cytokines that play an important role in the pathogenesis of SARS-CoV2 pneumonia, namely IL-6 (-572 G/C, intron 2A/G), and TNF-α (-376G/A, -308G/A).…”