TY - JOUR
T1 - Prognostic Genetic Markers for Thrombosis in COVID-19 Patients
T2 - A Focused Analysis on D-Dimer, Homocysteine and Thromboembolism
AU - Abu-Farha, Mohamed
AU - Al-Sabah, Salman
AU - Hammad, Maha M.
AU - Hebbar, Prashantha
AU - Channanath, Arshad Mohamed
AU - John, Sumi Elsa
AU - Taher, Ibrahim
AU - Almaeen, Abdulrahman
AU - Ghazy, Amany
AU - Mohammad, Anwar
AU - Abubaker, Jehad
AU - Arefanian, Hossein
AU - Al-Mulla, Fahd
AU - Thanaraj, Thangavel Alphonse
N1 - Funding Information:
This research was funded by Kuwait Foundation for Advancement in Sciences, grant number KFAS PN20-93MM-02.
Funding Information:
Grillet, F., Behr, J., Calame, P., Aubry, S., and Delabrousse, E. (2020). Acute pulmonary embolism associated with COVID-19 pneumonia detected by pulmonary CT angiography. Radiology 296, E186–E188. doi:10.1148/radiol.2020201544 Hebbar, P., Abu-Farha, M., Alkayal, F., Nizam, R., Elkum, N., Melhem, M., et al. (2020). Genome-wide association study identifies novel risk variants from RPS6KA1, CADPS, VARS, and DHX58 for fasting plasma glucose in Arab population. Sci. Rep. 10 (1), 152. doi:10.1038/s41598-019-57072-9 Helms, J., Tacquard, C., Severac, F., Leonard-Lorant, I., Ohana, M., Delabranche, X., et al. (2020). High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Medicine 46 (6), 1089–1098. doi:10.1007/s00134-020-06062-x Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., et al. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet (London, England) 395 (10223), 497–506. doi:10.1016/s0140-6736(20)30183-5 Iba, T., Levy, J. H., Levi, M., Connors, J. M., and Thachil, J. (2020). Coagulopathy of coronavirus disease 2019. Critical care medicine. doi:10.1097/ccm. 0000000000004458 Behring, instrumentation labs, Janssen, Merck, and Octapharma. Dr. Connors’ institution received funding from CSL Behring; received funding from Abbott (consulting), Bristol-Myers Squibb (consulting), and Portola (scientific advisory board). The remaining authors have disclosed that they do not have any potential conflicts of interest.
Publisher Copyright:
© Copyright © 2020 Abu-Farha, Al-Sabah, Hammad, Hebbar, Channanath, John, Taher, Almaeen, Ghazy, Mohammad, Abubaker, Arefanian, Al-Mulla and Thanaraj.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12/9
Y1 - 2020/12/9
N2 - COVID-19 is caused by Severe Acute Respiratory Syndrome Coronavirus-2, which has infected over thirty eight million individuals worldwide. Emerging evidence indicates that COVID-19 patients are at a high risk of developing coagulopathy and thrombosis, conditions that elevate levels of D-dimer. It is believed that homocysteine, an amino acid that plays a crucial role in coagulation, may also contribute to these conditions. At present, multiple genes are implicated in the development of these disorders. For example, single-nucleotide polymorphisms (SNPs) in FGG, FGA, and F5 mediate increases in D-dimer and SNPs in ABO, CBS, CPS1 and MTHFR mediate differences in homocysteine levels, and SNPs in TDAG8 associate with Heparin-induced Thrombocytopenia. In this study, we aimed to uncover the genetic basis of the above conditions by examining genome-wide associations and tissue-specific gene expression to build a molecular network. Based on gene ontology, we annotated various SNPs with five ancestral terms: pulmonary embolism, venous thromboembolism, vascular diseases, cerebrovascular disorders, and stroke. The gene-gene interaction network revealed three clusters that each contained hallmark genes for D-dimer/fibrinogen levels, homocysteine levels, and arterial/venous thromboembolism with F2 and F5 acting as connecting nodes. We propose that genotyping COVID-19 patients for SNPs examined in this study will help identify those at greatest risk of complications linked to thrombosis.
AB - COVID-19 is caused by Severe Acute Respiratory Syndrome Coronavirus-2, which has infected over thirty eight million individuals worldwide. Emerging evidence indicates that COVID-19 patients are at a high risk of developing coagulopathy and thrombosis, conditions that elevate levels of D-dimer. It is believed that homocysteine, an amino acid that plays a crucial role in coagulation, may also contribute to these conditions. At present, multiple genes are implicated in the development of these disorders. For example, single-nucleotide polymorphisms (SNPs) in FGG, FGA, and F5 mediate increases in D-dimer and SNPs in ABO, CBS, CPS1 and MTHFR mediate differences in homocysteine levels, and SNPs in TDAG8 associate with Heparin-induced Thrombocytopenia. In this study, we aimed to uncover the genetic basis of the above conditions by examining genome-wide associations and tissue-specific gene expression to build a molecular network. Based on gene ontology, we annotated various SNPs with five ancestral terms: pulmonary embolism, venous thromboembolism, vascular diseases, cerebrovascular disorders, and stroke. The gene-gene interaction network revealed three clusters that each contained hallmark genes for D-dimer/fibrinogen levels, homocysteine levels, and arterial/venous thromboembolism with F2 and F5 acting as connecting nodes. We propose that genotyping COVID-19 patients for SNPs examined in this study will help identify those at greatest risk of complications linked to thrombosis.
KW - coagulopathy
KW - COVID-19
KW - d-dimer
KW - heparin
KW - homocysteine
KW - pulmonary embolism
KW - thrombocytopenia
KW - venous thromboembolism
UR - http://www.scopus.com/inward/record.url?scp=85098096155&partnerID=8YFLogxK
U2 - 10.3389/fphar.2020.587451
DO - 10.3389/fphar.2020.587451
M3 - Review article
AN - SCOPUS:85098096155
VL - 11
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
SN - 1663-9812
M1 - 587451
ER -