SELP Asp603Asn and severe thrombosis in COVID-19 males.

COVID-19 / complications Down-Regulation Female Humans Male Middle Aged P-Selectin / genetics Point Mutation SARS-CoV-2 / isolation & purification Thrombosis / etiology
Anti-selectin P monoclonal antibodies COVID-19 P-selectin Thromboembolism Thrombus Venous thromboembolism

Journal

Journal of hematology & oncology
ISSN: 1756-8722
Titre abrégé: J Hematol Oncol
Pays: England
ID NLM: 101468937

Informations de publication

Date de publication:
16 08 2021
Historique:
received: 01 06 2021
accepted: 03 08 2021
entrez: 17 8 2021
pubmed: 18 8 2021
medline: 25 8 2021
Statut: epublish

Résumé

Thromboembolism is a frequent cause of severity and mortality in COVID-19. However, the etiology of this phenomenon is not well understood. A cohort of 1186 subjects, from the GEN-COVID consortium, infected by SARS-CoV-2 with different severity was stratified by sex and adjusted by age. Then, common coding variants from whole exome sequencing were mined by LASSO logistic regression. The homozygosity of the cell adhesion molecule P-selectin gene (SELP) rs6127 (c.1807G > A; p.Asp603Asn) which has been already associated with thrombotic risk is found to be associated with severity in the male subcohort of 513 subjects (odds ratio = 2.27, 95% Confidence Interval 1.54-3.36). As the SELP gene is downregulated by testosterone, the odd ratio is increased in males older than 50 (OR 2.42, 95% CI 1.53-3.82). Asn/Asn homozygotes have increased D-dimers values especially when associated with poly Q ≥ 23 in the androgen receptor (OR 3.26, 95% CI 1.41-7.52). These results provide a rationale for the repurposing of antibodies against P-selectin as adjuvant therapy in rs6127 male homozygotes especially if older than 50 or with an impaired androgen receptor.

Identifiants

DOI: 10.1186/s13045-021-01136-9 PMID: 34399825 PMC: PMC8365289
pubmed: 34399825
doi: 10.1186/s13045-021-01136-9
pii: 10.1186/s13045-021-01136-9
pmc: PMC8365289
doi:

Substances chimiques

P-Selectin 0
SELP protein, human 0

Types de publication

Letter Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

123

Commentaires et corrections

Type : ErratumIn

Informations de copyright

© 2021. The Author(s).

Références

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Auteurs

Chiara Fallerini (C)

Medical Genetics Unit, University of Siena, Policlinico Le Scotte, Viale Bracci, 2, 53100, Siena, Italy.
Department of Medical Biotechnologies, Med Biotech Hub and Competence Center, University of Siena, Siena, Italy.

Sergio Daga (S)

Medical Genetics Unit, University of Siena, Policlinico Le Scotte, Viale Bracci, 2, 53100, Siena, Italy.
Department of Medical Biotechnologies, Med Biotech Hub and Competence Center, University of Siena, Siena, Italy.

Elisa Benetti (E)

Department of Medical Biotechnologies, Med Biotech Hub and Competence Center, University of Siena, Siena, Italy.

Nicola Picchiotti (N)

Department of Mathematics, University of Pavia, Pavia, Italy.
DIISM-SAILAB, University of Siena, Siena, Italy.

Kristina Zguro (K)

Department of Medical Biotechnologies, Med Biotech Hub and Competence Center, University of Siena, Siena, Italy.

Francesca Catapano (F)

Medical Genetics Unit, University of Siena, Policlinico Le Scotte, Viale Bracci, 2, 53100, Siena, Italy.
Department of Medical Biotechnologies, Med Biotech Hub and Competence Center, University of Siena, Siena, Italy.

Virginia Baroni (V)

Medical Genetics Unit, University of Siena, Policlinico Le Scotte, Viale Bracci, 2, 53100, Siena, Italy.
Department of Medical Biotechnologies, Med Biotech Hub and Competence Center, University of Siena, Siena, Italy.

Simone Lanini (S)

National Institute for the Infectious Diseases "L. Spallanzani", Rome, Italy.

Alessandro Bucalossi (A)

Stem Cell Transplant and Cellular Therapy Unit, University Hospital, Siena, Italy.

Giuseppe Marotta (G)

Stem Cell Transplant and Cellular Therapy Unit, University Hospital, Siena, Italy.

Francesca Colombo (F)

Istituto di Tecnologie Biomediche - Consiglio Nazionale delle Ricerche, Segrate, MI, Italy.

Margherita Baldassarri (M)

Medical Genetics Unit, University of Siena, Policlinico Le Scotte, Viale Bracci, 2, 53100, Siena, Italy.
Department of Medical Biotechnologies, Med Biotech Hub and Competence Center, University of Siena, Siena, Italy.

Francesca Fava (F)

Medical Genetics Unit, University of Siena, Policlinico Le Scotte, Viale Bracci, 2, 53100, Siena, Italy.
Department of Medical Biotechnologies, Med Biotech Hub and Competence Center, University of Siena, Siena, Italy.
Genetica Medica, Azienda Ospedaliero-Universitaria Senese, Siena, Italy.

Giada Beligni (G)

Medical Genetics Unit, University of Siena, Policlinico Le Scotte, Viale Bracci, 2, 53100, Siena, Italy.
Department of Medical Biotechnologies, Med Biotech Hub and Competence Center, University of Siena, Siena, Italy.

Laura Di Sarno (L)

Medical Genetics Unit, University of Siena, Policlinico Le Scotte, Viale Bracci, 2, 53100, Siena, Italy.
Department of Medical Biotechnologies, Med Biotech Hub and Competence Center, University of Siena, Siena, Italy.

Diana Alaverdian (D)

Medical Genetics Unit, University of Siena, Policlinico Le Scotte, Viale Bracci, 2, 53100, Siena, Italy.
Department of Medical Biotechnologies, Med Biotech Hub and Competence Center, University of Siena, Siena, Italy.

Maria Palmieri (M)

Medical Genetics Unit, University of Siena, Policlinico Le Scotte, Viale Bracci, 2, 53100, Siena, Italy.
Department of Medical Biotechnologies, Med Biotech Hub and Competence Center, University of Siena, Siena, Italy.

Susanna Croci (S)

Medical Genetics Unit, University of Siena, Policlinico Le Scotte, Viale Bracci, 2, 53100, Siena, Italy.
Department of Medical Biotechnologies, Med Biotech Hub and Competence Center, University of Siena, Siena, Italy.

Andrea M Isidori (AM)

Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.

Simone Furini (S)

Department of Medical Biotechnologies, Med Biotech Hub and Competence Center, University of Siena, Siena, Italy.

Elisa Frullanti (E)

Medical Genetics Unit, University of Siena, Policlinico Le Scotte, Viale Bracci, 2, 53100, Siena, Italy.
Department of Medical Biotechnologies, Med Biotech Hub and Competence Center, University of Siena, Siena, Italy.

Alessandra Renieri (A)

Medical Genetics Unit, University of Siena, Policlinico Le Scotte, Viale Bracci, 2, 53100, Siena, Italy. alessandra.renieri@unisi.it.
Department of Medical Biotechnologies, Med Biotech Hub and Competence Center, University of Siena, Siena, Italy. alessandra.renieri@unisi.it.
Genetica Medica, Azienda Ospedaliero-Universitaria Senese, Siena, Italy. alessandra.renieri@unisi.it.
ORCID: 0000-0002-0846-9220

Francesca Mari (F)

Medical Genetics Unit, University of Siena, Policlinico Le Scotte, Viale Bracci, 2, 53100, Siena, Italy.
Department of Medical Biotechnologies, Med Biotech Hub and Competence Center, University of Siena, Siena, Italy.
Genetica Medica, Azienda Ospedaliero-Universitaria Senese, Siena, Italy.

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Classifications MeSH

questionsmedicales.fr › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Pneumopathie infectieuse › Pneumopathie virale › COVID-19 › SELP Asp603Asn and severe thrombosis in COVID-19 males.
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Régulation négative › SELP Asp603Asn and severe thrombosis in COVID-19 males.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › SELP Asp603Asn and severe thrombosis in COVID-19 males.
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › SELP Asp603Asn and severe thrombosis in COVID-19 males.
questionsmedicales.fr › Facteurs biologiques › Antigènes › Antigènes de surface › Molécules d'adhérence cellulaire › Sélectines › Sélectine P › SELP Asp603Asn and severe thrombosis in COVID-19 males.
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Mutation ponctuelle › SELP Asp603Asn and severe thrombosis in COVID-19 males.
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN à brin positif › Nidovirales › Coronaviridae › Coronavirus › Betacoronavirus › Virus du SRAS › SARS-CoV-2 › SELP Asp603Asn and severe thrombosis in COVID-19 males.
questionsmedicales.fr › Maladies cardiovasculaires › Maladies vasculaires › Embolie et thrombose › Thrombose › SELP Asp603Asn and severe thrombosis in COVID-19 males.