The rs17713054 and rs1800629 polymorphisms of genes LZTFL1 and TNF are associated with COVID-19 severity

Traspov AA1, Minashkin MM1, Poyarkov SV1, Komarov AG2, Shtinova IA2, Speshilov GI2, Karbyshev IA2, Pozdniakova NV1, Godkov MA3
About authors

1 Sistema BioTech LLC, 109235 Moscow, Russia

2 State Budget Institution Of Health Of The City Of Moscow "Diagnostic Center (Center For Laboratory Research) Of The Department Of Health Of The City Of Moscow" Russian Federation, , Moscow

3 Sklifosovskiy Research Institute for Emergency Medical Aid, Moscow, Russia

Correspondence should be addressed: Natalia V. Pozdnyakova
1 Kurjanovskaja, 34, korp. 11, Moscow, Russia; ur.hcetoibametsis@avokayndzop.n

About paper

Funding: the study was supported by the major Sistema BioTech LLC shareholder, the Sistema Public Joint Stock Financial Corporation. The study was funded by the Moscow Department of Health as part of the double blind clinical trial.

Acknowledgements: the authors express their gratitude to Antipova YuO, Deputy Head of the Moscow Department of Health, for organizing the blind clinical trial of COVID-19 severity and the patients of the Diagnostic Center (Center of Laboratory Testing) of the Moscow Department of Health for the provided biomaterial samples.

Author contribution: Pozdnyakova NV, Poyarkov SV — study concept and design; Minashkin MM — molecular genetic research, laboratory tests; Poyarkov SV, Traspov AA — literature review, manuscript writing; Traspov AA — statistical processing of the results, manuscript editing; Komarov AG — project management, planning the experiment, data analysis; Shtinova IA, Speshilov GI, Karbyshev IA — providing clinical data and metadata; Godkov MA — control over clinical sample collection at the Sklifosovsky Research Institute for Emergency Medicine, providing anonymized data.

Compliance with ethical standards: the study did not need to be approved by the Ethics Committee because of dealing with anonymized patient data and the double blind study format.

Received: 2022-11-18 Accepted: 2022-12-14 Published online: 2022-12-28

Both genetic and non-genetic factors are responsible for high interindividual variability in response to SARS-CoV-2. Despite the fact that multiple genetic polymorphisms have been identified as risk factors of severe COVID-19, such polymorphisms are still insufficiently studied in the Russian population. The study was aimed to identify genetic determinants associated with severe COVID-19 in the sample of patients from the Russian Federation. The correlation of the rs17713054 polymorphism in gene LZTFL1 and rs1800629 polymorphism in gene TNF (tumor necrosis factor) with the COVID-19 severity was assessed. DNA samples obtained from 713 patients (324 males and 389 females) aged 18‒95 with COVID-19 of varying severity were analyzed.  The rs1800629 polymorphism of gene TNF (OR = 1.5; p = 0.02) and rs17713054 polymorphism of gene LZTFL1 (OR = 1.60; p = 0.0043) were identified as risk factors of severe disease. The TNF polymorphism rs1800629 and LZTFL1 polymorphism rs17713054 could be considered as potential predictive biomarkers. The rs17713054 G > A polymorphism was strongly associated with severe disease. In the future the findings may provide the basis for the development of test-systems for prediction of the risk of severe viral respiratory diseases.

Keywords: SNP, TNF, COVID-19, SARS-CoV-2, LZTFL1, severity, host genetics determinants