Letter abstract
Nature Genetics 40, 546 - 552 (2008)
Published online: 28 April 2008 | doi:10.1038/ng.134
Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass
Enrico Petretto1,2,11, Rizwan Sarwar1,11, Ian Grieve1, Han Lu1, Mande K Kumaran1, Phillip J Muckett1, Jonathan Mangion1, Blanche Schroen1, Matthew Benson1, Prakash P Punjabi3, Sanjay K Prasad3, Dudley J Pennell3, Chris Kiesewetter3, Elena S Tasheva4, Lolita M Corpuz4, Megan D Webb4, Gary W Conrad4, Theodore W Kurtz5, Vladimir Kren6,7, Judith Fischer8, Norbert Hubner8, Yigal M Pinto9, Michal Pravenec6,7, Timothy J Aitman1,10 & Stuart A Cook1,3
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 transcript2 (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.
- Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK.
- Division of Epidemiology, Public Health and Primary Care, Faculty of Medicine, Imperial College, Praed Street, London, W2 1PG, UK.
- National Heart and Lung Institute, Imperial College, Dovehouse Street, London, SW3 6LY, UK.
- Division of Biology, 116 Ackert Hall, Kansas State University, Manhattan, Kansas 66506-4901, USA.
- Department of Laboratory Medicine, University of California, San Francisco, California 94143-0134, USA.
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Institute of Physiology, Czech Academy of Sciences and Centre for Applied Genomics, Víde
ská 1083, 142 20 Prague 4, Czech Republic. - Charles University in Prague, Institute of Biology and Medical Genetics of the First Faculty of Medicine and General Teaching Hospital, Albertov 4, 128 00 Prague 2, Czech Republic.
- Max-Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, Berlin-Buch, 13125, Germany.
- Heart Failure Research Center, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
- Section of Molecular Genetics and Rheumatology, Division and Faculty of Medicine, Imperial College, Hammersmith Hospital, Du Cane Road, London, W12 0NN.
- These authors contributed equally to this work.
Correspondence to: Timothy J Aitman1,10 e-mail: t.aitman@csc.mrc.ac.uk
Correspondence to: Stuart A Cook1,3 e-mail: stuart.cook@imperial.ac.uk
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