Study indicates that gene variant and stress can lead to dangerous heart condition

By Al Saint Jacques, MDLinx
Published November 28, 2016

Key Takeaways

A faulty gene that could set off a dangerous heart condition in otherwise healthy people if they are placed in highly stressful situations has been detected in approximately 1% of the population, according to research partly funded by the British Heart Foundation (BHF) and published November 21st in the journal Nature Genetics.

These findings indicate that approximately 75 million people worldwide could be at risk for developing heart failure if their hearts are placed under abnormal stress. Stress caused by pregnancy, a viral infection of the heart, alcoholism, or high blood pressure could potentially trigger the heart problems, according to researchers at Imperial College London and the MRC Clinical Sciences Centre (MRC-CSC), who studied both mice and people.

This international collaborative study 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.

DCM 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.

“We now know that the heart of a healthy individual with titin gene mutation lives in a compensated state and that the main heart pumping chamber is slightly bigger,” explained Professor Stuart Cook, who led the study and who is head of the Cardiovascular Genetics and Genomics group within Genetics & Imaging at the National Heart and Lung Institute (NHLI) and Professor of Clinical & Molecular Cardiology at Imperial College London. “Our next step is to find out the specific genetic factors or environmental triggers, such as alcohol or viral infection that may put certain people with titin mutations at risk of heart failure.”

In their study, 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%) 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 mice that suggest titin mutations, even in the absence of DCM, are having an impact on the heart but that this starts in a very subtle way.

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

“Most people with titin mutations live a long and healthy life, but some will develop DCM, 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,” explained Professor Sir Nilesh Samani, Medical Director at the British Heart Foundation.

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

Find out more about the BHF’s work to beat heart disease at

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