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SELP Asp603Asn and severe thrombosis in COVID-19 males.
Fallerini, Chiara; Daga, Sergio; Benetti, Elisa; Picchiotti, Nicola; Zguro, Kristina; Catapano, Francesca; Baroni, Virginia; Lanini, Simone; Bucalossi, Alessandro; Marotta, Giuseppe; Colombo, Francesca; Baldassarri, Margherita; Fava, Francesca; Beligni, Giada; Di Sarno, Laura; Alaverdian, Diana; Palmieri, Maria; Croci, Susanna; Isidori, Andrea M; Furini, Simone; Frullanti, Elisa; Renieri, Alessandra; Mari, Francesca.
  • Fallerini C; Medical Genetics Unit, University of Siena, Policlinico Le Scotte, Viale Bracci, 2, 53100, Siena, Italy.
  • Daga S; Department of Medical Biotechnologies, Med Biotech Hub and Competence Center, University of Siena, Siena, Italy.
  • Benetti E; Medical Genetics Unit, University of Siena, Policlinico Le Scotte, Viale Bracci, 2, 53100, Siena, Italy.
  • Picchiotti N; Department of Medical Biotechnologies, Med Biotech Hub and Competence Center, University of Siena, Siena, Italy.
  • Zguro K; Department of Medical Biotechnologies, Med Biotech Hub and Competence Center, University of Siena, Siena, Italy.
  • Catapano F; Department of Mathematics, University of Pavia, Pavia, Italy.
  • Baroni V; DIISM-SAILAB, University of Siena, Siena, Italy.
  • Lanini S; Department of Medical Biotechnologies, Med Biotech Hub and Competence Center, University of Siena, Siena, Italy.
  • Bucalossi A; Medical Genetics Unit, University of Siena, Policlinico Le Scotte, Viale Bracci, 2, 53100, Siena, Italy.
  • Marotta G; Department of Medical Biotechnologies, Med Biotech Hub and Competence Center, University of Siena, Siena, Italy.
  • Colombo F; Medical Genetics Unit, University of Siena, Policlinico Le Scotte, Viale Bracci, 2, 53100, Siena, Italy.
  • Baldassarri M; Department of Medical Biotechnologies, Med Biotech Hub and Competence Center, University of Siena, Siena, Italy.
  • Fava F; National Institute for the Infectious Diseases "L. Spallanzani", Rome, Italy.
  • Beligni G; Stem Cell Transplant and Cellular Therapy Unit, University Hospital, Siena, Italy.
  • Di Sarno L; Stem Cell Transplant and Cellular Therapy Unit, University Hospital, Siena, Italy.
  • Alaverdian D; Istituto di Tecnologie Biomediche - Consiglio Nazionale delle Ricerche, Segrate, MI, Italy.
  • Palmieri M; Medical Genetics Unit, University of Siena, Policlinico Le Scotte, Viale Bracci, 2, 53100, Siena, Italy.
  • Croci S; Department of Medical Biotechnologies, Med Biotech Hub and Competence Center, University of Siena, Siena, Italy.
  • Isidori AM; Medical Genetics Unit, University of Siena, Policlinico Le Scotte, Viale Bracci, 2, 53100, Siena, Italy.
  • Furini S; Department of Medical Biotechnologies, Med Biotech Hub and Competence Center, University of Siena, Siena, Italy.
  • Frullanti E; Genetica Medica, Azienda Ospedaliero-Universitaria Senese, Siena, Italy.
  • Renieri A; Department of Medical Biotechnologies, Med Biotech Hub and Competence Center, University of Siena, Siena, Italy.
  • Mari F; Medical Genetics Unit, University of Siena, Policlinico Le Scotte, Viale Bracci, 2, 53100, Siena, Italy.
J Hematol Oncol ; 14(1): 123, 2021 08 16.
Article in English | MEDLINE | ID: covidwho-2258652
ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Thrombosis / P-Selectin / COVID-19 Type of study: Cohort study / Etiology study / Observational study / Prognostic study Topics: Long Covid / Variants Limits: Female / Humans / Male / Middle aged Language: English Journal: J Hematol Oncol Journal subject: Hematology / Neoplasms Year: 2021 Document Type: Article Affiliation country: S13045-021-01136-9

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Thrombosis / P-Selectin / COVID-19 Type of study: Cohort study / Etiology study / Observational study / Prognostic study Topics: Long Covid / Variants Limits: Female / Humans / Male / Middle aged Language: English Journal: J Hematol Oncol Journal subject: Hematology / Neoplasms Year: 2021 Document Type: Article Affiliation country: S13045-021-01136-9