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Cappadona, Claudio; Paraboschi, Elvezia Maria; Ziliotto, Nicole; Bottaro, Sandro; Rimoldi, Valeria; Gerussi, Alessio; Azimonti, Andrea; Brenna, Daniele; Brunati, Andrea; Cameroni, Charlotte; Campanaro, Giovanni; Carloni, Francesca; Cavadini, Giacomo; Ciravegna, Martina; Composto, Antonio; Converso, Giuseppe; Corbella, Pierluigi; D’Eugenio, Davide; Dal Rì, Giovanna; Di Giorgio, Sofia Maria; Grondelli, Maria Chiara; Guerrera, Lorenza; Laffoucriere, Georges; Lando, Beatrice; [...]

MEDTEC Students against Coronavirus: Investigating the Role of Hemostatic Genes in the Predisposition to COVID-19 Severity

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  • Medientyp: E-Artikel
  • Titel: MEDTEC Students against Coronavirus: Investigating the Role of Hemostatic Genes in the Predisposition to COVID-19 Severity
  • Beteiligte: Cappadona, Claudio; Paraboschi, Elvezia Maria; Ziliotto, Nicole; Bottaro, Sandro; Rimoldi, Valeria; Gerussi, Alessio; Azimonti, Andrea; Brenna, Daniele; Brunati, Andrea; Cameroni, Charlotte; Campanaro, Giovanni; Carloni, Francesca; Cavadini, Giacomo; Ciravegna, Martina; Composto, Antonio; Converso, Giuseppe; Corbella, Pierluigi; D’Eugenio, Davide; Dal Rì, Giovanna; Di Giorgio, Sofia Maria; Grondelli, Maria Chiara; Guerrera, Lorenza; Laffoucriere, Georges; Lando, Beatrice; [...]
  • Erschienen: MDPI AG, 2021
  • Erschienen in: Journal of Personalized Medicine, 11 (2021) 11, Seite 1166
  • Sprache: Englisch
  • DOI: 10.3390/jpm11111166
  • ISSN: 2075-4426
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of the coronavirus disease 2019 (COVID-19) pandemic. Besides virus intrinsic characteristics, the host genetic makeup is predicted to account for the extreme clinical heterogeneity of the disease, which is characterized, among other manifestations, by a derangement of hemostasis associated with thromboembolic events. To date, large-scale studies confirmed that genetic predisposition plays a role in COVID-19 severity, pinpointing several susceptibility genes, often characterized by immunologic functions. With these premises, we performed an association study of common variants in 32 hemostatic genes with COVID-19 severity. We investigated 49,845 single-nucleotide polymorphism in a cohort of 332 Italian severe COVID-19 patients and 1668 controls from the general population. The study was conducted engaging a class of students attending the second year of the MEDTEC school (a six-year program, held in collaboration between Humanitas University and the Politecnico of Milan, allowing students to gain an MD in Medicine and a Bachelor’s Degree in Biomedical Engineering). Thanks to their willingness to participate in the fight against the pandemic, we evidenced several suggestive hits (p < 0.001), involving the PROC, MTHFR, MTR, ADAMTS13, and THBS2 genes (top signal in PROC: chr2:127192625:G:A, OR = 2.23, 95%CI = 1.50–3.34, p = 8.77 × 10−5). The top signals in PROC, MTHFR, MTR, ADAMTS13 were instrumental for the construction of a polygenic risk score, whose distribution was significantly different between cases and controls (p = 1.62 × 10−8 for difference in median levels). Finally, a meta-analysis performed using data from the Regeneron database confirmed the contribution of the MTHFR variant chr1:11753033:G:A to the predisposition to severe COVID-19 (pooled OR = 1.21, 95%CI = 1.09–1.33, p = 4.34 × 10−14 in the weighted analysis).
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