Journal Article

SELP Asp603Asn and severe thrombosis in COVID-19 males

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

2021

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Androgen receptors / Androgens / Anti-selectin P monoclonal antibodies / Blood platelets / Cancer Research / Cell adhesion molecules / Coronaviruses / COVID-19 / COVID-19 - complications / COVID-19 - genetics / Development and progression / Down-Regulation / Endothelium / Etiology / Female / Gene expression / Haplotypes / Health aspects / Hematology / Homozygotes / Humans / Infections / Letter to the Editor / Male / Medicine / Medicine & Public Health / Middle Aged / Monoclonal antibodies / Mortality / Oncology / P-selectin / P-Selectin - genetics / Point Mutation / Polymorphism / SARS-CoV-2 - isolation & purification / Severe acute respiratory syndrome coronavirus 2 / Testosterone / Thromboembolism / Thrombosis / Thrombosis - etiology / Thrombosis - genetics / Thrombus / Venous thromboembolism