Missense Variants of von Willebrand Factor in the Background of COVID-19 Associated Coagulopathy.
Genes (Basel)
; 14(3)2023 02 28.
Article
em En
| MEDLINE
| ID: mdl-36980889
ABSTRACT
COVID-19 associated coagulopathy (CAC), characterized by endothelial dysfunction and hypercoagulability, evokes pulmonary immunothrombosis in advanced COVID-19 cases. Elevated von Willebrand factor (vWF) levels and reduced activities of the ADAMTS13 protease are common in CAC. Here, we aimed to determine whether common genetic variants of these proteins might be associated with COVID-19 severity and hemostatic parameters. A set of single nucleotide polymorphisms (SNPs) in the vWF (rs216311, rs216321, rs1063856, rs1800378, rs1800383) and ADAMTS13 genes (rs2301612, rs28729234, rs34024143) were genotyped in 72 COVID-19 patients. Cross-sectional cohort analysis revealed no association of any polymorphism with disease severity. On the other hand, analysis of variance (ANOVA) uncovered associations with the following clinical parameters (1) the rs216311 T allele with enhanced INR (international normalized ratio); (2) the rs1800383 C allele with elevated fibrinogen levels; and (3) the rs1063856 C allele with increased red blood cell count, hemoglobin, and creatinine levels. No association could be observed between the phenotypic data and the polymorphisms in the ADAMTS13 gene. Importantly, in silico protein conformational analysis predicted that these missense variants would display global conformational alterations, which might affect the stability and plasma levels of vWF. Our results imply that missense vWF variants might modulate the thrombotic risk in COVID-19.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transtornos da Coagulação Sanguínea
/
Fator de von Willebrand
/
COVID-19
Tipo de estudo:
Etiology_studies
/
Observational_studies
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Prevalence_studies
/
Prognostic_studies
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Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Genes (Basel)
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Hungria