Scientists discover new heart attack genes

Posted by ap507 at Mar 08, 2016 10:52 AM |
BHF-funded discovery could lead to new statin-like treatments to prevent heart attacks

Issued by the British Heart Foundation

Scientists have identified two new genes that are associated with a person’s risk of coronary heart disease (CHD), thanks to research part-funded by the British Heart Foundation (BHF) and the National Institute for Health Research (NIHR). The findings, published in the New England Journal of Medicine (1) may lead to the discovery of new therapies to prevent heart attacks.

The international team, including researchers at the University of Leicester, looked at the DNA of more than 190,000 people, including those collected as part of the BHF Family Heart Study (2) between 2000 and 2005.

The researchers found that changes in the DNA code which alter a gene called ANGPTL4 were associated with a reduced risk of CHD, while errors in the SVEP1 gene were linked to an increased risk of CHD. CHD is responsible for nearly 70,000 deaths every year, making it the UK’s single biggest killer. Most deaths from CHD are caused by a heart attack (3).

ANGPTL4 affects triglyceride levels by blocking an enzyme called lipoprotein lipase (LPL) involved in removing a type of fat, called triglycerides, from the blood stream. The researchers also discovered a non-functioning form of the ANGPTL4 gene. People with this form of ANGPTL4 also had significantly reduced triglyceride levels in the bloodstream and a 53 per cent lower risk of CHD.

The findings prove alterations in ANGPTL4 are directly linked with reduced levels of triglyceride, as well as a reduced risk of CHD. The research adds to the body of evidence linking triglycerides with CHD, and identifies a potential new target for developing preventive therapies to reduce CHD risk by lowering triglycerides in a similar fashion to statins, which reduce CHD risk by lowering cholesterol levels.

The mechanism by which alterations in the SVEP1 gene affects CHD risk, in contrast, remains a mystery. The function of the SVEP1 gene is poorly understood. The researchers found a small association between the SVEP1 alterations and higher blood pressure, a major risk factor for CHD, but whether this is sufficient to explain the effect on CHD risk is unclear.

BHF Professor Sir Nilesh Samani, from the University of Leicester, is a lead researcher on this study and the BHF Family Heart Study. He said:

“The findings of this study are potentially very important. Until now many of the DNA alterations we have identified that affect CHD are in regulatory regions of our DNA which are less easy to target in terms of developing new treatments. Here, by implicating specific genes and the proteins they produce we are a step nearer developing much-required new treatments.

“Going forward we hope that we will be able to use this new information to develop new therapies to reduce a person’s likelihood of developing coronary heart disease and, ultimately, of having a heart attack.”

Dr Shannon Amoils, Senior Research Advisor at the British Heart Foundation, which funded the study, said:

“It’s long been debated whether triglyceride fats in the blood are directly linked to coronary heart disease. This large genetic study provides strong additional evidence to suggest there is a link between how the body processes triglycerides and coronary heart disease. 

“This study opens up opportunities for more research to find new treatments to prevent coronary heart disease, which could complement current therapies like statins, which lower another type of fat, cholesterol. “Promising discoveries like these are possible because of people's generous donations to the BHF combined with government research funding. Your support allows UK scientists to be at the heart of international efforts like this to finally beat heart disease.”

The research was an international collaboration between BHF-funded researchers at Leicester, also supported by the NIHR, and principal researchers at the Broad Institute at Massachusetts Institute of Technology, the Technical University of Munich and University of Lubeck in Germany, Queen Mary University London and  University of Cambridge, and several others.

Find out more about how donations to the BHF are helping fight heart disease at bhf.org.uk/research

ENDS

To request interviews or for more information please call the BHF press office on newsdesk@bhf.org.uk

Notes to editors

1) Stitziel NO, et al. Investigators from the Myocardial Infarction Genetics and CARDIoGRAM Exome Consortia. Coding variation in ANGPTL4, LPL, and SVEP1 and the risk of coronary disease. The New England Journal of Medicine. March 2, 2016.

Found here: http://www.nejm.org/doi/full/10.1056/NEJMoa1507652#t=article

2) BHF Family Heart Study: http://www.ncbi.nlm.nih.gov/pubmed/16380912

3) Statistics: https://www.bhf.org.uk/research/heart-statistics

British Heart Foundation

Coronary heart disease is the UK’s single biggest killer. For over 50 years we’ve pioneered research that’s transformed the lives of people living with heart and circulatory conditions. Our work has been central to the discoveries of vital treatments that are changing the fight against heart disease. But so many people still need our help. From babies born with life-threatening heart problems to the many Mums, Dads and Grandparents who survive a heart attack and endure the daily battles of heart failure. Every pound raised, minute of your time and donation to our shops will help make a difference to people’s lives.

Find out more at bhf.org.uk

The University of Leicester is led by discovery and innovation – an international centre for excellence renowned for research, teaching and broadening access to higher education. The University of Leicester is ranked among the top one per cent of universities in the world by the THE World University Rankings and also among the top 100 leading international universities in the world. It is among the top 25 universities in the Times Higher Education REF Research Power rankings with 75% of research adjudged to be internationally excellent with wide-ranging impacts on society, health, culture, and the environment.

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