One in 1,000 people may carry gene putting them at risk of rare heart condition

An estimated one in 1,000 people could carry a genetic variant which puts them at risk of a rare and potentially fatal heart condition, according to a study.

The figure is “higher than expected”, researchers said, and while many people will not go on to develop the disease, identifying those who do as early as possible could allow for it to be treated more effectively.

Cardiac transthyretin (ATTR) amyloidosis happens when the liver produces faulty transthyretin (TTR) proteins, which change shape and form clumps in the heart.

This makes it harder for the heart to pump blood and can eventually lead to heart failure.

Many people with these variants will not go on to develop disease. However, it is important to try to identify those who do as early as we can, as there are promising new medicines that can effectively treat the condition, and acting earlier with these medicines is likely to help patients more

The study by University College London (UCL) and Queen Mary University of London used data from the UK Biobank to analyse the genes of 469,789 people in the UK.

ATTR amyloidosis can be caused by a mutation in the TTR gene, but can also develop in people without the mutation.

The hereditary form is more common in people with black African ancestry and in certain populations in Portugal , Japan and Sweden, researchers said.

The study found about one in 1,000 people had a genetic variant with a link to ATTR amyloidosis.

The result was much higher among patients with African ancestry with about one in 23, or 4.3%, having genes linked to the disease.

Dr Luis Lopes, of the UCL Institute of Cardiovascular Science, said: “We found a higher than expected number of people in the UK with potentially harmful genetic variants linked to cardiac ATTR amyloidosis, an often fatal condition.

“Many people with these variants will not go on to develop disease. However, it is important to try to identify those who do as early as we can, as there are promising new medicines that can effectively treat the condition, and acting earlier with these medicines is likely to help patients more.”

Those with the variant – known as Val142Ile – were more likely to have heart rhythm problems, thickening of the heart muscle and heart failure.

However, hospital data showed just 2.8% of the group had been diagnosed with cardiac amyloidosis.

These findings could be an important step towards the earlier diagnosis of patients at risk of the condition so they can benefit from earlier treatment

Researchers said the findings – published in Jama Cardiology – “emphasise the need for clinical vigilance” to identify those at risk.

Dr Nay Aung, of the William Harvey Research Institute at Queen Mary University of London, added: “Our study showed that people carrying these potentially harmful variants have a two-to-three-fold increase in the risk of heart failure and cardiac rhythm issues.

“This again highlights the need for early detection and monitoring for disease progression.”

ATTR amyloidosis is estimated to effect between one in 120,000 and one in 830,000 people globally.

New treatments are being developed at the UCL Centre for Amyloidosis, including a gene-editing therapy which could stop disease progression.

Dr Sonya Babu-Narayan, associate medical director at the British Heart Foundation (BHF), said: “This research is a great example of the power of big population data studies, which can use national endeavours such as the UK Biobank and Our Future Health to reveal more about the genetic signatures of cardiovascular conditions than ever before.

“Thanks to nearly half a million UK Biobank participants, the study has shown that a gene linked to this unusual type of heart failure is more common than previously assumed.

“Transthyretin cardiac amyloidosis causes progressive heart failure which to date is devastating and difficult-to-treat.

“These findings could be an important step towards the earlier diagnosis of patients at risk of the condition so they can benefit from earlier treatment.”