Genome-Wide Expression Analysis Suggests Hypoxia-Triggered Hyper-Coagulation Leading to Venous Thrombosis at High Altitude

Thromb Haemost. 2018 Jul;118(7):1279-1295. doi: 10.1055/s-0038-1657770. Epub 2018 Jun 4.


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.

MeSH terms

  • Adult
  • Altitude*
  • Blood Coagulation / genetics*
  • Blood Coagulation Disorders / blood
  • Blood Coagulation Disorders / diagnosis
  • Blood Coagulation Disorders / genetics*
  • Case-Control Studies
  • Gene Expression Profiling / methods
  • Gene Regulatory Networks
  • Gene-Environment Interaction*
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Hypoxia / complications
  • Hypoxia / diagnosis
  • Hypoxia / genetics*
  • Male
  • Phenotype
  • Risk Assessment
  • Risk Factors
  • Transcriptome
  • Venous Thrombosis / blood
  • Venous Thrombosis / diagnosis
  • Venous Thrombosis / genetics*