Journal of Hematology & Oncology (Aug 2021)

SELP Asp603Asn and severe thrombosis in COVID-19 males

  • Chiara Fallerini,
  • Sergio Daga,
  • Elisa Benetti,
  • Nicola Picchiotti,
  • Kristina Zguro,
  • Francesca Catapano,
  • Virginia Baroni,
  • Simone Lanini,
  • Alessandro Bucalossi,
  • Giuseppe Marotta,
  • Francesca Colombo,
  • Margherita Baldassarri,
  • Francesca Fava,
  • Giada Beligni,
  • Laura Di Sarno,
  • Diana Alaverdian,
  • Maria Palmieri,
  • Susanna Croci,
  • Andrea M. Isidori,
  • Simone Furini,
  • Elisa Frullanti,
  • GEN-COVID Multicenter Study,
  • Alessandra Renieri,
  • Francesca Mari

DOI
https://doi.org/10.1186/s13045-021-01136-9
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 4

Abstract

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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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