Around 600,000 in UK carry faulty gene that could lead to heart failure



A new study from scientists at Imperial College London suggests a gene variant can trigger heart failure when the organ is under stress.

The research showed that around one in 100 people carry a faulty gene which could trigger a dangerous heart condition in seemingly healthy people, if the heart is placed under abnormal stress, such as through pregnancy or high blood pressure.

The work, which was part-funded by the British Heart Foundation (BHF), was carried out by researchers at Imperial College London and the MRC Clinical Sciences Centre (MRC-CSC).

We found that those with mutations have an enlarged heart, and in a pattern similar to that seen in heart failure patients. This may impact as many as 35 million people around the world.

– Dr Antonio de Marvao

Study author

The team, who studied both rats and people, believe the findings suggest around 75 million people worldwide could be at risk of developing heart failure if their hearts are placed under abnormal stress. It may be that the stress caused by pregnancy, a viral infection of the heart, alcoholism or high blood pressure could trigger the heart problems.

The international collaboration, which included BHF-funded Professor Stuart Cook, involved looking at rats with a faulty version of a gene called titin.

They found that although the rats appeared healthy, placing abnormal stress on the heart triggered a rare heart muscle condition called dilated cardiomyopathy (DCM), which causes heart failure.

Dilated cardiomyopathy is a disease of the heart muscle where it becomes stretched and thin, and is unable to pump blood around the body efficiently. It affects 1 in 250 people in the UK and is the most common cause of heart transplant.

The researchers also looked at the genes of 1,400 healthy adult volunteers and created detailed 3D computer models using scans of their hearts at the MRC-CSC in London.

As expected, 14 people (1 per cent) had the titin gene mutation. From looking at the 3D heart models, the scientists found that healthy people with the titin mutations had a slightly enlarged heart, compared with those without the mutations.

This supports the findings in rats which suggest titin mutations, even in the absence of dilated cardiomyopathy, are having an impact on the heart.

Research is now underway to find out which genetic factors or environmental triggers may put people with titin mutations at risk of heart failure.

Next steps

Professor Stuart Cook, who led the study, is head of the Cardiovascular Genetics and Genomics group within Genetics & Imaging at the National Heart and Lung Institute, and Professor of Clinical & Molecular Cardiology at Imperial College London.

He said: "We now know that the heart of a healthy individual with the titin gene mutation lives in a compensated state, and that the heart’s main pumping chamber is slightly bigger.

“Our next step is to find out which are the specific genetic factors or environmental triggers, such as alcohol or viral infection, may put certain people with titin mutations at risk of heart failure.”

Dr Antonio de Marvao, clinical lecturer at Imperial College London and the MRC Clinical Sciences Centre, added: “Our previous work showed that mutations in the titin gene are very common in people diagnosed with heart failure. But until now it wasn't known if these are ‘silent' gene changes or changes that can adversely affect the heart.

"Using state-of-the-art cardiac MRI scans we created extremely detailed 3D “virtual hearts” from the scans of 1400 healthy adults. We found that those with mutations have an enlarged heart, and in a pattern similar to that seen in heart failure patients.

"This may impact as many as 35 million people around the world. In future work we will investigate if the heart function of our volunteers is indeed impaired, by MRI scanning them as they exercise on a bike.”

Professor Sir Nilesh Samani, Medical Director at the British Heart Foundation, which part-funded the study, said: "Most people with titin mutations live a long and healthy life, but some will develop dilated cardiomyopathy, a heart condition which can lead for heart failure. This excellent research shows us that there is much more to this condition than we originally thought.

“We can now use this knowledge to identify preventable or avoidable factors that trigger the condition in those who carry titin mutations, and also develop new treatments which target the genetic basis of the disease."


Schafer, Marvao et al. "Titin truncating variants affect heart function in disease cohorts and the general population" Nature Genetics (2016).

Adapted from a press release by the British Heart Foundation and MRC Clinical Science Centre

See the press release of this article



Kate Wighton

Kate Wighton
Communications Division

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