Integrated Genomic Approaches Implicate Osteoglycin (Ogn) in the Regulation of Left Ventricular Mass

Overview

Journal Nat Genet

Specialty Genetics

Date 2008 Apr 30

PMID 18443592

Citations 80

Authors

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

Timothy J Aitman

Stuart A Cook

Affiliations

Soon will be listed here.

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.

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