Genome-Wide Expression Analysis Suggests Hypoxia-Triggered Hyper-Coagulation Leading to Venous Thrombosis at High Altitude
| Autor: | Neha Gupta, Prathima Arvind, Velu Nair, Bhuvnesh Kumar, Tathagata Chatterjee, Babita Kumari, Jiny Nair, Mohammad Z. Ashraf, Anita Sahu, Prabhash Kumar Jha, Manish Sharma, Tarun Tyagi, Jayashree Shanker, Nitin Bajaj, Amit Prabhakar |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Male Angiogenin Genome-wide association study Biology Risk Assessment 03 medical and health sciences Risk Factors Gene expression medicine Humans Gene Regulatory Networks Genetic Predisposition to Disease cardiovascular diseases Platelet activation Hypoxia Gene Blood Coagulation Venous Thrombosis Altitude Gene Expression Profiling Hematology Hypoxia (medical) Blood Coagulation Disorders Solute carrier family Gene expression profiling 030104 developmental biology Phenotype Case-Control Studies Cancer research Gene-Environment Interaction medicine.symptom Transcriptome Genome-Wide Association Study |
| Zdroj: | Thrombosis and haemostasis. 118(7) |
| ISSN: | 2567-689X |
| Popis: | Venous thromboembolism (VTE), a multi-factorial disease, is the third most common cardiovascular disease. Established genetic and acquired risk factors are responsible for the onset of VTE. High altitude (HA) also poses as an additional risk factor, predisposing individuals to VTE; however, its molecular mechanism remains elusive. This study aimed to identify genes/pathways associated with the pathophysiology of deep vein thrombosis (DVT) at HA. Gene expression profiling of DVT patients, who developed the disease, either at sea level or at HA-DVT locations, resulted in differential expression of 378 and 875 genes, respectively. Gene expression profiles were subjected to bioinformatic analysis, followed by technical and biological validation of selected genes using quantitative reverse transcription-polymerase chain reaction. Both gene ontology and pathway analysis showed enrichment of genes involved in haemostasis and platelet activation in HA-DVT patients with the most relevant pathway being ‘response to hypoxia’. Thus, given the environmental condition the differential expression of hypoxia-responsive genes (angiogenin, ribonuclease, RNase A family, 5; early growth response 1; lamin A; matrix metallopeptidase 14 [membrane-inserted]; neurofibromin 1; PDZ and LIM domain 1; procollagen-lysine 1, 2-oxoglutarate 5-dioxygenase 1; solute carrier family 6 [neurotransmitter transporter, serotonin], member 4; solute carrier family 9 [sodium/hydrogen exchanger], member 1; and TEK tyrosine kinase, endothelial) in HA-DVT could be a determining factor to understand the pathophysiology of DVT at HA. |
| Databáze: | OpenAIRE |
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