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 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 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.