title: Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass.
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.
authors.affiliation: Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK.
authors.forename: Enrico
authors.initials: E
authors.lastname: Petretto
authors.forename: Rizwan
authors.initials: R
authors.lastname: Sarwar
authors.forename: Ian
authors.initials: I
authors.lastname: Grieve
authors.forename: Han
authors.initials: H
authors.lastname: Lu
authors.forename: Mande K
authors.initials: MK
authors.lastname: Kumaran
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Muckett
authors.forename: Jonathan
authors.initials: J
authors.lastname: Mangion
authors.forename: Blanche
authors.initials: B
authors.lastname: Schroen
authors.forename: Matthew
authors.initials: M
authors.lastname: Benson
authors.forename: Prakash P
authors.initials: PP
authors.lastname: Punjabi
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Prasad
authors.forename: Dudley J
authors.initials: DJ
authors.lastname: Pennell
authors.forename: Chris
authors.initials: C
authors.lastname: Kiesewetter
authors.forename: Elena S
authors.initials: ES
authors.lastname: Tasheva
authors.forename: Lolita M
authors.initials: LM
authors.lastname: Corpuz
authors.forename: Megan D
authors.initials: MD
authors.lastname: Webb
authors.forename: Gary W
authors.initials: GW
authors.lastname: Conrad
authors.forename: Theodore W
authors.initials: TW
authors.lastname: Kurtz
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kren
authors.forename: Judith
authors.initials: J
authors.lastname: Fischer
authors.forename: Norbert
authors.initials: N
authors.lastname: Hubner
authors.forename: Yigal M
authors.initials: YM
authors.lastname: Pinto
authors.forename: Michal
authors.initials: M
authors.lastname: Pravenec
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Aitman
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Cook
mesh_terms: D000818:Animals; D001024:Aortic Valve Stenosis / Q000150:complications / Q000235:genetics; D001794:Blood Pressure / Q000235:genetics; D002874:Chromosome Mapping; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D023281:Genomics; D006023:Glycoproteins / Q000235:genetics / Q000502:physiology*; D006352:Heart Ventricles / Q000033:anatomy & histology* / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000235:genetics; D017379:Hypertrophy, Left Ventricular / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009929:Organ Size / Q000235:genetics; D040641:Quantitative Trait Loci; D051381:Rats / Q000235:genetics*; D011922:Rats, Mutant Strains
chemical_list: D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C063488:OGN protein, human; C512906:Ogn protein, mouse; C512905:Ogn protein, rat