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

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

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 characteri...

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Autores principales: Claudio Cappadona, Elvezia Maria Paraboschi, Nicole Ziliotto, Sandro Bottaro, Valeria Rimoldi, Alessio Gerussi, Andrea Azimonti, Daniele Brenna, Andrea Brunati, Charlotte Cameroni, Giovanni Campanaro, Francesca Carloni, Giacomo Cavadini, Martina Ciravegna, Antonio Composto, Giuseppe Converso, Pierluigi Corbella, Davide D’Eugenio, Giovanna Dal Rì, Sofia Maria Di Giorgio, Maria Chiara Grondelli, Lorenza Guerrera, Georges Laffoucriere, Beatrice Lando, Leandro Lopedote, Benedetta Maizza, Elettra Marconi, Carlotta Mariola, Guia Margherita Matronola, Luca Maria Menga, Giulia Montorsi, Antonio Papatolo, Riccardo Patti, Lorenzo Profeta, Vera Rebasti, Alice Smidili, Sofia Maria Tarchi, Francesco Carlo Tartaglia, Gaia Tettamanzi, Elena Tinelli, Riccardo Stuani, Cristiana Bolchini, Linda Pattini, Pietro Invernizzi, Frauke Degenhardt, Andre Franke, Stefano Duga, Rosanna Asselta
Formato: article
Lenguaje:EN
Publicado: MDPI AG 2021
Materias:
SARS-CoV-2
COVID-19
hemostatic genes
association analysis
polygenic risk score
meta-analysis
Medicine
R
Acceso en línea:https://doaj.org/article/89d5e1d3059744e4a40cb014fbeedad5
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Sumario: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 (<i>p</i> < 0.001), involving the <i>PROC</i>, <i>MTHFR</i>, <i>MTR</i>, <i>ADAMTS13</i>, and <i>THBS2</i> genes (top signal in <i>PROC</i>: chr2:127192625:G:A, OR = 2.23, 95%CI = 1.50–3.34, <i>p</i> = 8.77 × 10<sup>−5</sup>). The top signals in <i>PROC</i>, <i>MTHFR</i>, <i>MTR</i>, <i>ADAMTS13</i> were instrumental for the construction of a polygenic risk score, whose distribution was significantly different between cases and controls (<i>p</i> = 1.62 × 10<sup>−8</sup> for difference in median levels). Finally, a meta-analysis performed using data from the Regeneron database confirmed the contribution of the <i>MTHFR</i> variant chr1:11753033:G:A to the predisposition to severe COVID-19 (pooled OR = 1.21, 95%CI = 1.09–1.33, <i>p</i> = 4.34 × 10<sup>−14</sup> in the weighted analysis).

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