The main pumping chamber in the hearts of healthy people with the titin mutation are slightly bigger, study finds.
A report in Nature Genetics describes how researchers from the United Kingdom, Singapore, and Germany came to this conclusion after studying the gene mutations - called titin-truncating variants - in rats and people.
In their paper, the authors explain that the gene variants commonly cause dilated cardiomyopathy, an inherited heart condition that leads to heart failure and affects around 1 in 250 people worldwide.
It is also known that around 1 percent of the general population carry the variants, "where they may be silent," note the authors.
Dilated cardiomyopathy is where the heart enlarges, causing the muscle to become stretched and thin, which, in turn, impairs the organ's ability to pump blood and oxygen around the body.
However, when the researchers studied healthy rats with the faulty genes, they found that while the animals appeared healthy, putting abnormal stress on their hearts triggered dilated cardiomyopathy.
The researchers also studied 1,400 healthy adults.
From state-of-the-art magnetic resonance imaging (MRI) scans, they created detailed 3-D computer models of the participants' hearts, and they also looked at their genes.
Hearts of faulty gene carriers 'primed to fail'
As expected, the genetic analysis showed that 14 participants - 1 percent - carried the titin gene variants.
However, the 3-D heart models of carriers of the gene variants showed their hearts were slightly enlarged compared with those of participants without the variants. The researchers also observed that the enlarged hearts showed a pattern similar to that seen in heart failure patients.
Fast facts about heart failure
- About 5.7 million American adults are living with heart failure
- Heart failure contributed to around 1 in 9 American deaths in 2009
- Heart failure costs the U.S. an estimated $30.7 billion each year.
This result supported what the researchers found in the rats, suggesting that even in the absence of dilated cardiomyopathy, carrying the titin variants appears to affect the heart.
Stuart Cook, a professor of clinical and molecular cardiology at Imperial College London in the U.K., where he also heads a Cardiovascular Genetics and Genomics group at the National Heart and Lung Institute, is one of the study supervisors. He says:
"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."
The finding may help to unravel the paradox of why it is that around 1 percent of people worldwide live with the faulty gene with no apparent effect.
The researchers believe the answer is that the hearts of people with the titin gene variants are "primed to fail" if they experience a second hit - a trigger that stresses the heart.
First author Sebastian Schäfer, an assistant professor and senior research fellow at the National Heart Centre Singapore, says they could directly observe the effect gene mutations had on titin production which, in turn, affects the heart. Titin is the largest protein in the human body that causes dilated cardiomyopathy.
"Even though the heart appears healthy initially," he explains, "it reacts to this genetic stress on many levels such as changes to its gene expression and energy source."
"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."
Prof. Stuart Cook