Petretto Enrico, Sarwar Rizwan, Grieve Ian, Lu Han, Kumaran Mande K, Muckett Phillip J, Mangion Jonathan, Schroen Blanche, Benson Matthew, Punjabi Prakash P, Prasad Sanjay K, Pennell Dudley J, Kiesewetter Chris, Tasheva Elena S, Corpuz Lolita M, Webb Megan D, Conrad Gary W, Kurtz Theodore W, Kren Vladimir, Fischer Judith, Hubner Norbert, Pinto Yigal M, Pravenec Michal, Aitman Timothy J, Cook Stuart A
Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK.
Nat Genet. 2008 May;40(5):546-52. doi: 10.1038/ng.134.
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.
左心室质量（LVM）和心脏基因表达是由心脏内在和外在因素共同调节的复杂性状。为了剖析LVM的主要决定因素，我们结合了大鼠心脏转录组的表达定量性状位点1和定量性状转录本（QTT）分析。使用这些方法和体外功能测定，我们确定骨形成蛋白（Ogn）是大鼠LVM的主要候选调节因子，Ogn蛋白表达增加与LVM升高相关。我们还对人类心脏进行了全基因组QTT分析，发现在22000个转录本中，OGN转录本丰度与LVM的相关性最高。我们进一步证实了Ogn在Ogn基因敲除小鼠体内对LVM的调节作用。综上所述，这些数据表明Ogn是大鼠、小鼠和人类LVM的关键调节因子，并提示Ogn可改变对高血压和主动脉狭窄等外在因素的肥厚反应。
