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SELP Asp603Asn and severe thrombosis in COVID-19 males

Chiara Fallerini1,2, Sergio Daga1,2, Elisa Benetti2

  • 1Medical Genetics Unit, University of Siena, Policlinico Le Scotte, Viale Bracci, 2, 53100, Siena, Italy.

Journal of Hematology & Oncology
|August 17, 2021
PubMed

Insights

COVID-19 severity and mortality are linked to blood clots. A specific gene variant in males, particularly those over 50, increases this risk, suggesting targeted P-selectin therapies.

Area of Science:

  • Genetics and Genomics
  • Infectious Diseases
  • Cardiovascular Medicine

Background:

  • Thromboembolism is a major contributor to COVID-19 severity and mortality.
  • The underlying causes of COVID-19-associated thromboembolism remain unclear.
  • This study investigated genetic factors influencing COVID-19 severity in relation to thrombosis.

Discussion:

  • The homozygosity of the SELP gene variant rs6127 (Asp603Asn) is associated with increased COVID-19 severity in males.
  • This association is more pronounced in males over 50, potentially due to testosterone's downregulation of SELP.
  • Combined homozygosity for SELP rs6127 and specific androgen receptor genotypes (poly Q ≥ 23) further elevates D-dimer levels, indicating heightened thrombotic risk.

Key Insights:

  • Identified a significant association between the SELP rs6127 variant and COVID-19 severity in males.
  • Demonstrated an age-dependent effect in males over 50, linked to hormonal regulation.
  • Revealed an interaction between SELP genotype and androgen receptor variants impacting thrombotic markers.

Outlook:

  • Suggests P-selectin targeted therapies, such as antibodies, as potential adjuvant treatments for high-risk male COVID-19 patients.
  • Highlights the need for personalized medicine approaches based on genetic profiling.
  • Further research into the role of sex hormones and genetic variants in COVID-19 pathogenesis is warranted.

Keywords:
Anti-selectin P monoclonal antibodiesCOVID-19P-selectinThromboembolismThrombusVenous thromboembolism

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