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Association of polymorphisms in tumor necrosis factors with SARS-CoV-2 infection and mortality rate: a case-control study and in silico analyses

J Med Virol. 2021 Nov 25. doi: 10.1002/jmv.27477. Online ahead of print.

ABSTRACT

As the present coronavirus disease 2019 (COVID-19) spreads and existing data suggested susceptibility factors for developing a severe course of the disease. This case-control experiment aimed to study the associations of genetic polymorphisms in tumor necrosis factors (TNFs) with COVID-19 and its mortality rate. A total of 550 participants (275 subjects and 275 controls) were enrolled. The tetra-ARMS-PCR technique was recruited to detect -308G>A TNFα and +252A>G TNFβ polymorphisms among the Iranian population. We demonstrated that participants carrying the G allele of TNFβ-252A/G, rs909253 A>G was more frequent in COVID-19 subjects compared to the healthy group and statistically increased the disease risk (OR=1.55, 95% CI=1.23-1.96, P<0.0001). At the same time, the A allele of TNFα-311A/G, rs1800629 G>A moderately decreased the risk of COVID-19 (OR=0.68, 95% CI=0.53-0.86, P<0.002). Also, we analyzed the various genotypes regarding the para-clinical and disorder severity; we found that the AA genotype of TNFβ-252A/G, rs909253 A>G, the CT scan pattern was different in comparison to cases in the AG genotype with P 1 <0.001. In addition, in the severe cases of COVID-19, leucocyte and neutrophil count and duration of ICU hospitalization in the death group have been significantly increased (P<0.001). Moreover, the TNFα-311A/G, rs1800629 G>A variant is likely to change the pattern of splicing factor sites. Our findings provided deep insights into the relationship between TNFα/TNFβ polymorphisms and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Replicated studies may give scientific evidence for exploring molecular mechanisms of COVID-19 in other ethnicities. This article is protected by copyright. All rights reserved.

PMID:34821383 | DOI:10.1002/jmv.27477

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