Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2008-05

AUTHORS

Enrico Petretto, Rizwan Sarwar, Ian Grieve, Han Lu, Mande K Kumaran, Phillip J Muckett, Jonathan Mangion, Blanche Schroen, Matthew Benson, Prakash P Punjabi, Sanjay K Prasad, Dudley J Pennell, Chris Kiesewetter, Elena S Tasheva, Lolita M Corpuz, Megan D Webb, Gary W Conrad, Theodore W Kurtz, Vladimir Kren, Judith Fischer, Norbert Hubner, Yigal M Pinto, Michal Pravenec, Timothy J Aitman, Stuart A Cook

ABSTRACT

Left ventricular mass (LVM) and cardiac gene expression are complex traits regulated by factors both intrinsic and extrinsic to the heart. To dissect the major determinants of LVM, we combined expression quantitative trait locus1 and quantitative trait transcript (QTT) analyses of the cardiac transcriptome in the rat. Using these methods and in vitro functional assays, we identified osteoglycin (Ogn) as a major candidate regulator of rat LVM, with increased Ogn protein expression associated with elevated LVM. We also applied genome-wide QTT analysis to the human heart and observed that, out of 22,000 transcripts, OGN transcript abundance had the highest correlation with LVM. We further confirmed a role for Ogn in the in vivo regulation of LVM in Ogn knockout mice. Taken together, these data implicate Ogn as a key regulator of LVM in rats, mice and humans, and suggest that Ogn modifies the hypertrophic response to extrinsic factors such as hypertension and aortic stenosis. More... »

PAGES

546-552

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ng.134

DOI

http://dx.doi.org/10.1038/ng.134

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1019220900

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/18443592


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