One gene that can cause the heart to become enlarged and another that can cause the kidney to become inflamed are revealed in parallel studies<em> - News Release </em>
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Imperial College London News Release
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1900 London time (BST) / 1400 US Eastern time
Monday 28 April 2008
A gene that can cause the heart to become enlarged, greatly increasing the risk of heart attacks and heart failure, is identified today in a new study.
A gene that can cause the kidney to become inflamed, which can lead to kidney failure, is also revealed in a parallel discovery.
The heart research, published in the journal Nature Genetics, reveals how a gene called osteoglycin (Ogn), which had not previously been linked with heart function, plays a key role in regulating heart growth. The study suggests that the gene can behave abnormally in some people, and that this can lead to the heart becoming abnormally enlarged.
The researchers hope that through understanding how enlarged hearts are linked to the workings of genes like Ogn, they will be able to develop new treatments for the condition, which affects a large proportion of those with high blood pressure, obesity and diabetes.
Scientists believe that enlarged hearts are caused by a combination of genetic factors and external stimuli such as high blood pressure and obesity. However, the role played by genes has remained largely unknown.
The researchers, from Imperial College London, the Medical Research Council (MRC), and other international institutions, hope that their findings will provide new avenues for treating people who either have an enlarged heart or are at risk of developing one. At present enlarged hearts can only be treated by lowering blood pressure.
The discovery of the Jund gene could offer a route for tackling the destruction of kidney tissue which can occur in lupus patients, causing renal failure
The study shows that Ogn regulates the growth of the heart's main pumping chamber, its left ventricle. If the left ventricle thickens, this creates a condition known as elevated Left Ventricular Mass (LVM), a major contributing factor for common heart diseases. When the heart is enlarged it needs more oxygen and becomes stiff. This can cause shortness of breath or lead to a heart attack.
The researchers found that higher than normal levels of kidney tissue which can occur in lupus patients, causing renal of Ogn were associated with the heart becoming enlarged in rats and mice and in humans.Dr Stuart Cook, one of the corresponding authors of the study from the MRC Clinical Sciences Centre and the National Heart and Lung Institute at Imperial College London, said:
"Enlarged hearts are very common. A person whose heart is enlarged is more likely to suffer a heart attack or heart failure than someone whose heart is a normal size. We can't currently treat the condition directly, so lowering a patient's blood pressure is the only option we have. Now that we are unravelling how genes control heart growth, we can gain a better understanding of common forms of heart disease. This should lead to new and more effective ways of treating people."
The study was primarily funded by the British Heart Foundation and the UK Department of Health.
The researchers first linked the Ogn gene with elevated LVM by looking at rat models and analysing how LVM related to the genetic makeup of rats with both elevated and normal LVM.
They then carried out the same analyses on samples from the human heart, volunteered by patients who had undergone cardiac surgery at Hammersmith Hospital, part of Imperial College Healthcare NHS Trust, and from a second group of patients from the Netherlands. These analyses showed that out of 22,000 possible genes, Ogn was the gene most strongly correlated with elevated LVM in humans.
Professor Tim Aitman, also a corresponding author of the study from the MRC Clinical Sciences Centre and Imperial College London, added: "This study shows how we can use the wealth of new genome technologies for analysing people's genes to gain a much greater understanding of common human disorders. We already knew that enlarged hearts were linked with conditions such as high blood pressure and obesity but figuring out the genetic causes as well could be key to working out how to treat the condition."
In a parallel development today, Professor Aitman, working with colleagues including Professor Terry Cook from Imperial College London, has identified a gene which controls the activity of a group of cells thought to be responsible for potentially severe inflammation of the kidney. The gene, also revealed in a study in Nature Genetics, is known as Jund and it could offer a route for tackling the auto-immune destruction of kidney tissue which can occur in lupus patients, causing renal failure.
Jund regulates the activity of macrophages, cells which help us fight infection by eating up cellular debris and pathogens, and stimulating immune cells. The new research showed that when these cells are overactive, they can destroy healthy kidney tissue.
Professor Aitman, who led the Medical Research Council team, said: "We are hoping that this discovery will allow us to find a new and effective way of treating this potentially fatal form of kidney failure. By reducing the activity of the Jund gene, we were able to reduce activity of inflammatory cells that can become overactive in certain diseases of the kidney. Such a therapy would be of obvious benefit to patients suffering from auto-immune diseases such as lupus. This would allow them to avoid dialysis and maintain their quality of life."
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Notes to editors:
1. "Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass" Nature Genetics, 28 April 2008
Corresponding authors: Stuart Cook and Tim Aitman (for full list of authors please see paper)
"Jund is a determinant of macrophage activation and is associated with glomerulonephritis susceptibility" Nature Genetics, 28 April 2008
Corresponding author: Tim Aitman (for full list of authors please see paper)
2. About Imperial College London
Imperial College London - rated the world’s fifth best university in the 2007 Times Higher Education Supplement University Rankings - is a science-based institution with a reputation for excellence in teaching and research that attracts 12,000 students and 6,000 staff of the highest international quality. Innovative research at the College explores the interface between science, medicine, engineering and business, delivering practical solutions that improve quality of life and the environment - underpinned by a dynamic enterprise culture. Website: www.imperial.ac.uk
3. About the Medical Research Council
The Medical Research Council supports the best scientific research to improve human health. Its work ranges from molecular level science to public health medicine and has led to pioneering discoveries in our understanding of the human body and the diseases which affect us all.
4. About the British Heart Foundation
The British Heart Foundation (BHF) is the nation's heart charity, dedicated to saving lives through pioneering research, patient care, campaigning for change and by providing vital information. But we urgently need help. We rely on donations of time and money to continue our life-saving work. Because together we can beat heart disease. For more information visit www.bhf.org.uk
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