Thromb Haemost 2018; 118(07): 1279-1295
DOI: 10.1055/s-0038-1657770
Stroke, Systemic or Venous Thromboembolism
Georg Thieme Verlag KG Stuttgart · New York

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

Prabhash Kumar Jha*
Defense Institute of Physiology and Allied Sciences, Defense Research and Development Organisation, Delhi, India
,
Anita Sahu*
Defense Institute of Physiology and Allied Sciences, Defense Research and Development Organisation, Delhi, India
,
Amit Prabhakar
Defense Institute of Physiology and Allied Sciences, Defense Research and Development Organisation, Delhi, India
,
Tarun Tyagi
Defense Institute of Physiology and Allied Sciences, Defense Research and Development Organisation, Delhi, India
,
Tathagata Chatterjee
Army Hospital (Research and Referral), New Delhi, India
,
Prathima Arvind
Thrombosis Research Institute, India, Bangalore, Karnataka, India
,
Jiny Nair
Thrombosis Research Institute, India, Bangalore, Karnataka, India
,
Neha Gupta
Defense Institute of Physiology and Allied Sciences, Defense Research and Development Organisation, Delhi, India
,
Babita Kumari
Defense Institute of Physiology and Allied Sciences, Defense Research and Development Organisation, Delhi, India
,
Velu Nair
Armed Forces Medical College, Pune, Maharashtra, India
,
Nitin Bajaj
Command Hospital (Western Command) Chandimandir, Panchkula, Haryana, India
,
Jayashree Shanker
Thrombosis Research Institute, India, Bangalore, Karnataka, India
,
Manish Sharma
Defense Institute of Physiology and Allied Sciences, Defense Research and Development Organisation, Delhi, India
,
Bhuvnesh Kumar
Defense Institute of Physiology and Allied Sciences, Defense Research and Development Organisation, Delhi, India
,
Mohammad Zahid Ashraf#
Defense Institute of Physiology and Allied Sciences, Defense Research and Development Organisation, Delhi, India
› Author Affiliations
Further Information

Publication History

29 December 2017

19 April 2018

Publication Date:
04 June 2018 (eFirst)

Abstract

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.

Authors' Contributions

P.K.J. and A.S. performed the experiments, analysed the data and wrote the manuscript; A.P. and B.K. performed the real-time PCR experiments; P.A., J.N. and J.S. performed the microarray experiments; T.C., N.B. and V.N. participated in the clinical part of the study; T.T., M.S. and N.G. edited the manuscript; M.Z.A. designed the study, interpreted the data and drafted the manuscript. P.K.J. and A.S. contributed equally to this study.


* These authors contributed equally to the manuscript.


# Present address: Department of Biotechnology, Jamia Millia Islamia, New Delhi-110025, India (e-mail: zashraf@jmi.ac.in).