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

Enrico Petretto, Rizwan Sarwar, Ian Grieve, Han Lu, Kumaran Kuppusamy Mande, 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 FischerNorbert Hubner, Yigal M. Pinto, Michal Pravenec, Timothy J. Aitman, Stuart A. Cook

    Research output: Contribution to journalArticlepeer-review

    118 Scopus citations

    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 ∼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.

    Original languageEnglish (US)
    Pages (from-to)546-552
    Number of pages7
    JournalNature Genetics
    Volume40
    Issue number5
    DOIs
    StatePublished - May 1 2008

    ASJC Scopus subject areas

    • Genetics

    Fingerprint

    Dive into the research topics of 'Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass'. Together they form a unique fingerprint.

    Cite this