A Singapore-UK-Germany research collaboration has discovered that the gene mutations responsible for dilated cardiomyopathy also affect the heart function of healthy individuals.
A Singapore-UK-Germany research collaboration has discovered that the gene mutations responsible for dilated cardiomyopathy also affect the heart function of healthy individuals.
Titin is the largest protein in the human body that causes dilated cardiomyopathy, a condition in which the heart muscle becomes weakened, enlarged and cannot pump blood efficiently. The condition is inherited and affects about 1 in 250 people worldwide.
It was previously thought that mutations in titin affect only patients with dilated cardiomyopathy. The researchers found that this was not the case. Around one per cent of the world's population, approximately 35 million people, carry this genetic mutation with no apparent effect.
The key, the team now believes, is that the hearts of such people may be "primed to fail" if they suffer a second hit, whether genetic or environmental.
Professor Stuart Cook, Tanoto Foundation Professor of Cardiovascular Medicine at the SingHealth Duke-NUS Academic Medical Centre and co-senior author of the paper, elaborated: "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."
The study was led by the National Heart Centre Singapore in collaboration with Duke-NUS Medical School, Medical Research Council Clinical Sciences Centre, Imperial College London and Max Delbrück Center for Molecular Medicine in the Helmholtz Association.
The researchers studied the effects of titin gene mutations in 2,495 patients with dilated cardiomyopathy. They also generated two rat models to understand the impact of these mutations on the molecular level and heart function. In addition, cardiac gene sequencing tests were performed in 1,409 healthy volunteers, coupled with 2D and 3D cardiac magnetic resonance imaging (MRI) that gave high resolution information on the heart size and shape of the study subjects.
Dr James Ware, Clinical Senior Lecturer in Genomic Medicine at Imperial College London and the MRC Clinical Sciences Centre, added: "For patients with dilated cardiomyopathy, this study has improved our understanding of the disease, revealed possible new targets for drugs and other new therapies, and importantly has improved our ability to diagnose the condition confidently with genetic tests.
Prof Cook added, "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."
The research paper was published in leading medical journal, Nature Genetics on 21 November 2016.
