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 per cent 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.
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 per cent – 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.
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 per cent 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.
“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
Source: Medical News Today