Prognostic Genetic Markers for Thrombosis in COVID-19 Patients: A Focused Analysis on D-Dimer, Homocysteine and Thromboembolism.
PMID 33362545 | PMCID PMC7756688 | DOI 10.3389/fphar.2020.587451 · Frontiers in pharmacology · 2020
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.
Validated evidence
| Type | Entity | Source evidence | Confidence | Extractor |
|---|---|---|---|---|
| gene | FGG | “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.” | 0.98 | hgnc_dict_v1 |
| gene | FGA | “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.” | 0.98 | hgnc_dict_v1 |
| gene | F5 | “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.” | 0.98 | hgnc_dict_v1 |
| gene | ABO | “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.” | 0.98 | hgnc_dict_v1 |
| gene | CBS | “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.” | 0.98 | hgnc_dict_v1 |
| gene | CPS1 | “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.” | 0.98 | hgnc_dict_v1 |
| gene | MTHFR | “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.” | 0.98 | hgnc_dict_v1 |
| phenotype | COVID-19 | “Prognostic Genetic Markers for Thrombosis in COVID-19 Patients: A Focused Analysis on D-Dimer, Homocysteine and Thromboembolism.” | 0.98 | phenotype_alias_lexicon_v2 |
| phenotype | stroke | “Based on gene ontology, we annotated various SNPs with five ancestral terms: pulmonary embolism, venous thromboembolism, vascular diseases, cerebrovascular disorders, and stroke.” | 0.98 | phenotype_alias_lexicon_v2 |
| phenotype | SARS | “COVID-19 is caused by Severe Acute Respiratory Syndrome Coronavirus-2, which has infected over thirty eight million individuals worldwide.” | 0.93 | phenotype_alias_lexicon_v2 |
| population | Population | “Prognostic Genetic Markers for Thrombosis in COVID-19 Patients: A Focused Analysis on D-Dimer, Homocysteine and Thromboembolism.” | 0.80 | saudi_context_rules_v1 |