Back to Journals » The Application of Clinical Genetics » Volume 8

ROCK2 and MYLK variants under hypobaric hypoxic environment of high altitude associate with high altitude pulmonary edema and adaptation

Authors Pandey P, Mohammad G, Singh Y, Pasha MQ

Received 9 June 2015

Accepted for publication 25 September 2015

Published 2 November 2015 Volume 2015:8 Pages 257—267


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Martin H. Maurer

Priyanka Pandey,1,2 Ghulam Mohammad,1,3 Yogendra Singh,1,2 MA Qadar Pasha1,2

1Functional Genomics Unit, CSIR-Institute of Genomics and Integrative Biology, Delhi, 2Department of Biotechnology, University of Pune, Ganeshkhind, Pune, Maharashtra, 3Department of Medicine, SNM Hospital, Leh, Ladakh, Jammu and Kashmir, India

Objective: To date, a major class of kinases, serine–threonine kinase, has been scantly investigated in stress-induced rare, fatal (if not treated early), and morbid disorder, high altitude pulmonary edema (HAPE). This study examined three major serine–threonine kinases, ROCK2, MYLK, and JNK1, along with six other genes, tyrosine hydroxylase, G-protein subunits GNA11 and GNB3, and alpha1 adrenergic receptor isoforms 1A, 1B, and 1D as candidate gene markers of HAPE and adaptation.
Methods: For this, 57 variants across these nine genes were genotyped in HAPE patients (n=225), HAPE controls (n=210), and highlanders (n=259) by Sequenom MS (TOF)-based MassARRAY® platform using iPLEX™ Gold technology. In addition, to study the gene expression, quantitative real-time polymerase chain reaction was performed in human peripheral blood mononuclear cells of the three study groups.
Results: A significant association was observed for C allele (ROCK2 single-nucleotide polymorphism, rs10929728) with HAPE (P=0.03) and C, T, and A alleles (MYLK single-nucleotide polymorphisms, rs11717814, rs40305, and rs820336) with both HAPE and adaptation (P=0.001, P=0.006, and P=0.02, respectively). ROCK2 88 kb GGGTTGGT haplotype was associated with lower risk of HAPE (P=0.0009). MYLK 7 kb haplotype CTA, composed of variant alleles, was associated with higher risk of HAPE (P=0.0006) and lower association with adaptation (P=1E–06), whereas haplotype GCG, composed of wild-type alleles, was associated with lower risk of HAPE (P=0.001) and higher association with adaptation (P=1E–06). Haplotype–haplotype and gene–gene interactions demonstrated a correlation in working of ROCK2 and MYLK.
Conclusion: The data suggest the association of ROCK2 with HAPE and MYLK with HAPE and adaptation in Indian population. The outcome has provided new insights into the physiology of HAPE and adaptation.

Keywords: adaptation, hypobaric hypoxia, ROCK2, MYLK, high altitude pulmonary edema, SNP

A Letter to the Editor has been received and published for this article.

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]