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

被引：134

作者：

Petretto, Enrico ^{[1
,2
]}

Sarwar, Rizwan ^{[1
]}

Grieve, Ian ^{[1
]}

Lu, Han ^{[1
]}

Kumaran, Mande K. ^{[1
]}

Muckett, Phillip J. ^{[1
]}

Mangion, Jonathan ^{[1
]}

Schroen, Blanche ^{[1
]}

Benson, Matthew ^{[1
]}

Punjabi, Prakash P. ^{[3
]}

Prasad, Sanjay K. ^{[3
]}

Pennell, Dudley J. ^{[3
]}

Kiesewetter, Chris ^{[3
]}

Tasheva, Elena S. ^{[4
]}

Corpuz, Lolita M. ^{[4
]}

Webb, Megan D. ^{[4
]}

Conrad, Gary W. ^{[4
]}

Kurtz, Theodore W. ^{[5
]}

Kren, Vladimir ^{[6
,7
,8
,9
]}

Fischer, Judith ^{[10
]}

Hubner, Norbert ^{[10
]}

Pinto, Yigal M. ^{[11
]}

Pravenec, Michal ^{[6
,7
,8
,9
]}

Aitman, Timothy J. ^{[1
,12
,13
]}

Cook, Stuart A. ^{[1
,3
]}

机构：

[1] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Fac Med, MRC,Clin Sci Ctr, London W12 0NN, England

[2] Univ London Imperial Coll Sci Technol & Med, Fac Med, Div Epidemiol Publ Hlth & Primary Care, London W2 1PG, England

[3] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London SW3 6LY, England

[4] Kansas State Univ, Div Biol, Manhattan, KS 66506 USA

[5] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA

[6] Acad Sci Czech Republic, Inst Physiol, CR-14220 Prague 4, Czech Republic

[7] Ctr Appl Genom, Prague 14220 4, Czech Republic

[8] Charles Univ Prague, Inst Biol & Med Genet, Fac Med 1, Prague 12800 2, Czech Republic

[9] Gen Teaching Hosp, Prague 12800 2, Czech Republic

[10] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany

[11] Univ Amsterdam, Acad Med Ctr, Heart Failure Res Ctr, NL-1105 AZ Amsterdam, Netherlands

[12] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Sect Mol Genet & Rheumatol, London W12 0NN, England

[13] Univ London Imperial Coll Sci Technol & Med, Fac Med, London W12 0NN, England

来源：

NATURE GENETICS | 2008年 / 40卷 / 05期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

D O I：

10.1038/ng.134

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 locus(1) and quantitative trait transcript(2) ( 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 similar to 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.

引用

页码：546 / 552

页数：7

共 30 条

[1] ECM remodeling in hypertensive heart disease [J].

Berk, Bradford C. ;

Fujiwara, Keigi ;

Lehoux, Stephanie .

JOURNAL OF CLINICAL INVESTIGATION, 2007, 117 (03) :568-575

[2] Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project [J].

Birney, Ewan ;

Stamatoyannopoulos, John A. ;

Dutta, Anindya ;

Guigo, Roderic ;

Gingeras, Thomas R. ;

Margulies, Elliott H. ;

Weng, Zhiping ;

Snyder, Michael ;

Dermitzakis, Emmanouil T. ;

Stamatoyannopoulos, John A. ;

Thurman, Robert E. ;

Kuehn, Michael S. ;

Taylor, Christopher M. ;

Neph, Shane ;

Koch, Christoph M. ;

Asthana, Saurabh ;

Malhotra, Ankit ;

Adzhubei, Ivan ;

Greenbaum, Jason A. ;

Andrews, Robert M. ;

Flicek, Paul ;

Boyle, Patrick J. ;

Cao, Hua ;

Carter, Nigel P. ;

Clelland, Gayle K. ;

Davis, Sean ;

Day, Nathan ;

Dhami, Pawandeep ;

Dillon, Shane C. ;

Dorschner, Michael O. ;

Fiegler, Heike ;

Giresi, Paul G. ;

Goldy, Jeff ;

Hawrylycz, Michael ;

Haydock, Andrew ;

Humbert, Richard ;

James, Keith D. ;

Johnson, Brett E. ;

Johnson, Ericka M. ;

Frum, Tristan T. ;

Rosenzweig, Elizabeth R. ;

Karnani, Neerja ;

Lee, Kirsten ;

Lefebvre, Gregory C. ;

Navas, Patrick A. ;

Neri, Fidencio ;

Parker, Stephen C. J. ;

Sabo, Peter J. ;

Sandstrom, Richard ;

Shafer, Anthony .

NATURE, 2007, 447 (7146) :799-816

[3] Practical value of cardiac magnetic resonance imaging for clinical quantification of aortic valve stenosis comparison with echocardiography [J].

Caruthers, SD ;

Lin, SJ ;

Brown, P ;

Watkins, MP ;

Williams, TA ;

Lehr, KA ;

Wickline, SA .

CIRCULATION, 2003, 108 (18) :2236-2243

[4] Transcriptional alterations in the left ventricle of three hypertensive rat models [J].

Cerutti, Catherine ;

Kurdi, Mazen ;

Bricca, Giampiero ;

Hodroj, Wassim ;

Paultre, Christian ;

Randon, Jacques ;

Gustin, Marie-Paule .

PHYSIOLOGICAL GENOMICS, 2006, 27 (03) :295-308

[5] ACC/AHA/ASE 2003 guideline update for the clinical application of Echocardiography: Summary article [J].

Cheitlin, MD ;

Armstrong, WF ;

Aurigemma, GP ;

Beller, GA ;

Bierman, FZ ;

Davis, JL ;

Douglas, PS ;

Faxon, DP ;

Gillam, LD ;

Kimball, TR ;

Kussmaul, WG ;

Pearlman, AS ;

Philbrick, JT ;

Rakowski, H ;

Thys, DM ;

Antman, EM ;

Smith, SC ;

Alpert, JS ;

Gregoratos, G ;

Anderson, JL ;

Hiratzka, LF ;

Faxon, DP ;

Hunt, SA ;

Fuster, V ;

Jacobs, AK ;

Gibbons, RJ ;

Russell, RO .

JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY, 2003, 16 (10) :1091-1110

[6] A20 is dynamically regulated in the heart and inhibits the hypertrophic response [J].

Cook, SA ;

Novikov, MS ;

Ahn, Y ;

Matsui, T ;

Rosenzweig, A .

CIRCULATION, 2003, 108 (06) :664-667

[7]

Cook SA, 1999, CIRC RES, V85, P940

[8] Genetical genomics in humans and model organisms [J].

de Koning, DJ ;

Haley, CS .

TRENDS IN GENETICS, 2005, 21 (07) :377-381

[9] Relations of left ventricular mass to demographic and hemodynamic variables in American Indians - The Strong Heart Study [J].

Devereux, RB ;

Roman, MJ ;

deSimone, G ;

OGrady, MJ ;

Paranicas, M ;

Yeh, JL ;

Fabsitz, RR ;

Howard, BV .

CIRCULATION, 1997, 96 (05) :1416-1423

[10] Discovery of expression QTLs using large-scale transcriptional profiling in human lymphocytes [J].

Goering, Harald H. H. ;

Curran, Joanne E. ;

Johnson, Matthew P. ;

Dyer, Thomas D. ;

Charlesworth, Jac ;

Cole, Shelley A. ;

Jowett, Jeremy B. M. ;

Abraham, Lawrence J. ;

Rainwater, David L. ;

Comuzzie, Anthony G. ;

Mahaney, Michael C. ;

Almasy, Laura ;

MacCluer, Jean W. ;

Kissebah, Ahmed H. ;

Collier, Gregory R. ;

Moses, Eric K. ;

Blangero, John .

NATURE GENETICS, 2007, 39 (10) :1208-1216

← 1 2 3 →