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

Research output: Contribution to journalArticle

  • 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
  • Stuart A Cook

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    Rights statement: Published in final edited form as: Nat Genet. May 2008; 40(5): 546–552.

    Accepted author manuscript, 1.21 MB, PDF document

http://www.nature.com/ng/journal/v40/n5/full/ng.134.html
Original languageEnglish
Pages (from-to)546-52
Number of pages7
JournalNature Genetics
Volume40
Issue number5
DOIs
Publication statusPublished - May 2008

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.

    Research areas

  • Animals, Aortic Valve Stenosis, Blood Pressure, Chromosome Mapping, Gene Expression Profiling, Gene Expression Regulation, Genomics, Glycoproteins, Heart Ventricles, Humans, Hypertension, Hypertrophy, Left Ventricular, Intercellular Signaling Peptides and Proteins, Mice, Mice, Knockout, Organ Size, Quantitative Trait Loci, Rats, Rats, Mutant Strains

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