1. Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass.
- Author
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Petretto E, Sarwar R, Grieve I, Lu H, Kumaran MK, Muckett PJ, Mangion J, Schroen B, Benson M, Punjabi PP, Prasad SK, Pennell DJ, Kiesewetter C, Tasheva ES, Corpuz LM, Webb MD, Conrad GW, Kurtz TW, Kren V, Fischer J, Hubner N, Pinto YM, Pravenec M, Aitman TJ, and Cook SA
- Subjects
- Animals, Aortic Valve Stenosis complications, Aortic Valve Stenosis genetics, Blood Pressure genetics, Chromosome Mapping, Gene Expression Regulation, Genomics, Glycoproteins genetics, Heart Ventricles metabolism, Humans, Hypertension complications, Hypertension genetics, Intercellular Signaling Peptides and Proteins genetics, Mice, Mice, Knockout, Organ Size genetics, Quantitative Trait Loci, Rats, Mutant Strains, Gene Expression Profiling, Glycoproteins physiology, Heart Ventricles anatomy & histology, Hypertrophy, Left Ventricular genetics, Intercellular Signaling Peptides and Proteins physiology, Rats genetics
- 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.
- Published
- 2008
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