Gene study targets heart failure
14 Jan 2015
A study conducted by researchers at Imperial College London (ICL) has revealed the gene mutations responsible for the heart condition dilated cardiomyopathy (DCM).
By sequencing the gene encoding the muscle protein ’titin’ in 5,267 people, scientists have identified which variations are linked to disease, providing information that will help screen high-risk patients and pave the way for more accurate diagnosis.
According to statistics, roughly one in 250 people have DCM which causes the heart muscle to become thin and weak, and can often leading to heart failure.
Though titin gene mutations are associated with DCM, researchers said many people have variations in the genetic code that are completely benign.
“We can use this information to screen patients’ relatives to identify those at risk of developing the disease
ICL study leader Stuart Cook
Through the ICL study, researchers are sorting the harmful mutations from the harmless ones, giving doctors a directory to interpret patients’ DNA sequences, the researchers said.
According to researchers, the information could also help experts develop therapies to prevent or treat heart disease caused by titin mutations.
Mutations in the titin gene that make the protein shorter, or truncated, are the most common cause of DCM, accounting for about a quarter of cases.
To conduct its study, the ICL research team, accompanied by researchers from the Royal Brompton & Harefield NHS Foundation Trust, sequenced the titin gene from healthy volunteers and patients with DCM, and analysed the levels of titin in samples of heart tissue.
According to results, the mutations that cause DCM occur at the far end of the gene sequence. Mutations in healthy individuals tend to occur in parts of the gene that are not included in the final protein, allowing titin to remain functional, the researchers said.
Stuart Cook, from the Medical Research Council (MRC) Clinical Sciences Centre at ICL, said: “These results give us a detailed understanding of the molecular basis for dilated cardiomyopathy.
“We can use this information to screen patients’ relatives to identify those at risk of developing the disease, and help them to manage their condition early.”
Likewise, Dudley Pennell, director of the NIHR Royal Brompton Cardiovascular Biomedical Research Unit, said the research reveals which genetic mutations are “bad” and which are there merely as “bystanders”.
“It will benefit patients with cardiomyopathy and enable us to reassure relatives who do not have the disease, allowing them to be discharged from clinic and preventing needless anxiety and unnecessary expensive tests,” Pennell said.
According to James Ware, who worked on the study, equivalent techniques could be applicable to other genes.
“One of the key features of our study is the very detailed characterisation of the participants’ hearts, using state-of-the-art cardiac MRI (CMR), which increases the power of our study. CMR was performed not only in our patients, but also in our control groups, allowing us to rigorously assess their heart status,” Ware said.
“We are applying similar techniques to a wide range of genes involved in inherited cardiac conditions, including heart muscle diseases and inherited heart rhythm problems,” he said.
