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

Item Type:Article
Title:Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass
Creators Name:Petretto, E. and Sarwar, R. and Grieve, I. and Lu, H. and Kumaran, M.K. and Muckett, P.J. and Mangion, J. and Schroen, B. and Benson, M. and Punjabi, P.P. and Prasad, S.K. and Pennell, D.J. and Kiesewetter, C. and Tasheva, E.S. and Corpuz, L.M. and Webb, M.D. and Conrad, G.W. and Kurtz, T.W. and Kren, V. and Fischer, J. and Huebner, N. and Pinto, Y.M. and Pravenec, M. and Aitman, T.J. and Cook, S.A.
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 locus 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 approximately 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.
Keywords:Aortic Valve Stenosis, Blood Pressure, Chromosome Mapping, Gene Expression Profiling, Gene Expression Regulation, Genomics, Glycoproteins, Heart Ventricles, Hypertension, Left Ventricular Hypertrophy, Intercellular Signaling Peptides and Proteins, Organ Size, Quantitative Trait Loci, Animals, Mice, Rats
Source:Nature Genetics
ISSN:1061-4036
Publisher:Nature Publishing Group (U.S.A.)
Volume:40
Number:5
Page Range:546-552
Date:May 2008
Official Publication:https://doi.org/10.1038/ng.134
PubMed:View item in PubMed

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