Around 1% of the population carries a genetic mutation which can have a strong impact on their heart health.
It all comes down to a special protein in the body called titin. Titin is responsible for making muscle stretchy and bendy. But a mutation in the TTN gene (which makes the titin protein) can cause the heart to fail because it causes the heart muscle to become weakened and enlarged, meaning it can’t pump blood around the body efficiently. This condition is known as dilated cardiomyopathy, and it affects about 1 in 250 people worldwide.
It was previously thought that the titin mutation would not affect people carrying the mutated gene, so long as it wasn’t expressed. However, new research from The National Heart Centre Singapore and others has shown that hearts of all 1% of people with the mutation could be at risk of heart failure, not just those in whom the gene is expressed.
The hearts of all these people may be “primed to fail” if they suffer another problem with their hearts, from the environment or their genetics, such as a family history of heart disease or poor lifestyle and diet, the researchers said. The results were published in the journal Nature Genetics.
The team studied the effects of titin gene mutations in 2,495 people with dilated cardiomyopathy, and also studied two rat models to take a closer look at the molecular level of affected hearts. Two-dimensional and three-dimensional MRI images showed patients’ hearts in greater detail.
“We could directly show the impact of the mutations on the titin protein production which has an impact on the heart,” Dr Sebastian Schäfer, first author of the study and Genetics professor at the National Heart Centre Singapore, said in a statement. “Even though the heart appears healthy initially, it reacts to this genetic stress on many levels such as changes to its gene expression and energy source.
He added that the heart can compensate for limited function until another stressor comes up.
“That’s when the heart fails, as it no longer has the capacity to react the same way a healthy heart does,” he said.
Professor Stuart Cook, a professor of cardiovascular medicine at the SingHealth Duke-NUS Academic Medical Centre and co-author of the paper said in a statement that hearts of a healthy people with the titin gene mutation live in a “compensated state” and have slightly enlarged heart chambers.
“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,” he said.