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Host genetic variants associated with COVID-19 reconsidered in a Slovak cohort

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SKERENOVA Maria CIBULKA Michal DANKOVA Zuzana HOLUBEKOVA Veronika KOLKOVA Zuzana LUCANSKY Vincent DVORSKA Dana KAPINOVA Andrea KRIVOSOVA Michaela PETRAS Martin BARANOVICOVA Eva BARANOVA Ivana NOVAKOVA Elena LIPTAK Peter BANOVCIN Peter BOBCAKOVA Anna ROSOLANKA Robert JANICKOVA Maria STANCLOVA Andrea GASPAR Ludovit CAPRNDA Martin PROSECKÝ Robert LABUDOVA Monika GABBASOV Zufar RODRIGO Luis KRUŽLIAK Peter LASABOVA Zora MATAKOVA Tatiana HALASOVA Erika

Rok publikování 2024
Druh Článek v odborném periodiku
Časopis / Zdroj Advances in Medical Sciences
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
www https://www.sciencedirect.com/science/article/pii/S1896112624000208?via%3Dihub
Doi http://dx.doi.org/10.1016/j.advms.2024.03.007
Klíčová slova Haplotypes; Host genetic risk factors; Immunoregulatory pathways; Severe acute respiratory syndrome coronavirus 2; Single nucleotide variants
Popis We present the results of an association study involving hospitalized coronavirus disease 2019 (COVID-19) patients with a clinical background during the 3rd pandemic wave of COVID-19 in Slovakia. Seventeen single nucleotide variants (SNVs) in the eleven most relevant genes, according to the COVID-19 Host Genetics Initiative, were investigated. Our study confirms the validity of the influence of LZTFL1 and 2 '-5 '-oligoadenylate synthetase (OAS)1/OAS3 genetic variants on the severity of COVID-19. For two LZTFL1 SNVs in complete linkage disequilibrium, rs17713054 and rs73064425, the odds ratios of baseline allelic associations and logistic regressions (LR) adjusted for age and sex ranged in the four tested designs from 2.04 to 2.41 and from 2.05 to 3.98, respectively. The OAS1/OAS3 haplotype 'gttg' carrying a functional allele G of splice-acceptor variant rs10774671 manifested its protective function in the Delta pandemic wave. Significant baseline allelic associations of two DPP9 variants in all tested designs and two IFNAR2 variants in the Omicron pandemic wave were not confirmed by adjusted LR. Nevertheless, adjusted LR showed significant associations of NOTCH4 rs3131294 and TYK2 rs2304256 variants with severity of COVID-19. Hospitalized patients' reported comorbidities were not correlated with genetic variants, except for obesity, smoking (IFNAR2), and hypertension (NOTCH4). The results of our study suggest that host genetic variations have an impact on the severity and duration of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Considering the differences in allelic associations between pandemic waves, they support the hypothesis that every new SARS-CoV-2 variant may modify the host immune response by reconfiguring involved pathways.

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