Rare gene mutations that increase the risk of a premature heart attack in middle age have been discovered by scientists. Men under 50 and women under 60 are twice as likely to have a heart attack if they have a faulty gene called APOA5. It causes levels of cholesterol and blood fats called triglycerides, which can cause clots, to rise. Men under 50 and women under 60 are twice as likely to have a heart attack (illustrated with a stock image) if they have a faulty gene called APOA5. It causes levels of cholesterol and blood fats called triglycerides, which can cause clots, to rise . Heart attacks are responsible for millions of deaths around the world and are triggered by both genetic and environmental factors, such as unhealthy lifestyles. Scientists from the Broad Institute, Massachusetts General Hospital and other institutions analysed the genomes of 10,000 people, half of whom suffered a heart attack early in life. Those that had the heart attacks were found to have mutations in the LDL receptor gene, confirming what has been known for decades – that high levels of LDL, or ‘bad cholesterol,' raises the risk of heart attack. The key finding, however, was that people carrying mutations in the APOA5 (apolipoprotein A-V) gene, have higher levels of blood triglycerides – or blood lipids - and a roughly two-fold increased risk of a heart attack. While the gene has been previously implicated in the condition, it has only now been confirmed using large-scale DNA sequencing to ‘definitively’ make the connection between APOA5 and heart attack risk. Scientists from the Broad Institute, Massachusetts General Hospital and other institutions analysed the genomes of 10,000 people, half of whom suffered a heart attack early in life. A stock image of a DNA sequence is pictured . ‘We simply wouldn't have made this critical connection without our careful and disciplined approach to whole exome sequencing [sequencing of the protein-coding portion of the genome] and subsequent data analysis,’ said Stacey Gabriel, a co-author of the Nature study and director of the Broad Institute's Genomics Platform. Researchers hope the findings could lead to new drugs to help reduce the number of heart attacks in middle age. Dr Sekar Kathiresan, a cardiologist at Massachusetts General Hospital in Boston, said: ‘Our APOA5 result tells us beyond LDL levels - which are well known to contribute to heart attack risk - abnormalities in triglyceride metabolism also play an important role. ‘This gives us an important window into the biology of the disease and also suggests potential new avenues for therapeutic development.’ The study follows other recent genetic discoveries including the identification of protective mutations in the APOC3 gene, that lower ‘bad fat’ levels and the risk of heart attack. There are some striking parallels between this new study and similar work conducted over 40 years ago, which was led by Nobel Prize winner Professor Joseph Goldstein. His study examined several hundred people from Seattle who had suffered a heart attack before the age of 60. Looking at the levels of fats in the blood, his researchers identified high cholesterol levels as the major link. The study has bolstered previous studies that found that LDL - the major carrier of cholesterol in the bloodstream - causes atherosclerosis (illustrated using computer artwork), where fats accumulate in blood vessels and lead to a heart attack . That work spurred decades of research trying to unravel the role of LDL - the major carrier of cholesterol in the bloodstream - in causing atherosclerosis, where fats accumulate in blood vessels and lead to a heart attack. Interestingly the second most common abnormality observed by Professor Goldstein and his colleagues was elevated blood triglycerides, but he was unable to explain this comprehensively at the time. Dr Kathiresan and his colleagues also found harmful LDL receptor mutations are roughly twice as common than had been estimated in the Goldstein study. He said: ‘In 1973 Goldstein’s work taught us what types of lipids in the blood are most important for early heart attack risk. Now after sequencing all of the genes in the genome we can directly point to the specific genes that are most important. There is remarkable consistency between the observations from 40 years ago and today.’ Only about five per cent of people who suffer a heart attack do so at a relatively young age. But tragically the first sign of illness in this minority is often a devastating heart attack inflicting significant damage to the heart and resulting in severe disability or even death. There are 230,000 heart attacks in the UK every year - with about one-in-ten proving fatal.
Scientists from the Broad Institute, Massachusetts General Hospital have pinpointed rare mutations in a gene called APOA5 .
Mutations increase a person's risk of having a heart attack early in life .
They disable the gene, while raising the levels of a type of fat in the blood .
While only five per cent of people who suffer a heart attack do so before 50, the first sign of illness is often the devastating attack itself .
Rare gene mutations that increase the risk of a premature heart attack in middle age have been discovered by scientists. Men under 50 and women under 60 are twice as likely to have a heart attack if they have a faulty gene called APOA5. It causes levels of cholesterol and blood fats called triglycerides, which can cause clots, to rise. Men under 50 and women under 60 are twice as likely to have a heart attack (illustrated with a stock image) if they have a faulty gene called APOA5. It causes levels of cholesterol and blood fats called triglycerides, which can cause clots, to rise . Heart attacks are responsible for millions of deaths around the world and are triggered by both genetic and environmental factors, such as unhealthy lifestyles. Scientists from the Broad Institute, Massachusetts General Hospital and other institutions analysed the genomes of 10,000 people, half of whom suffered a heart attack early in life. Those that had the heart attacks were found to have mutations in the LDL receptor gene, confirming what has been known for decades – that high levels of LDL, or ‘bad cholesterol,' raises the risk of heart attack. The key finding, however, was that people carrying mutations in the APOA5 (apolipoprotein A-V) gene, have higher levels of blood triglycerides – or blood lipids - and a roughly two-fold increased risk of a heart attack. While the gene has been previously implicated in the condition, it has only now been confirmed using large-scale DNA sequencing to ‘definitively’ make the connection between APOA5 and heart attack risk. Scientists from the Broad Institute, Massachusetts General Hospital and other institutions analysed the genomes of 10,000 people, half of whom suffered a heart attack early in life. A stock image of a DNA sequence is pictured . ‘We simply wouldn't have made this critical connection without our careful and disciplined approach to whole exome sequencing [sequencing of the protein-coding portion of the genome] and subsequent data analysis,’ said Stacey Gabriel, a co-author of the Nature study and director of the Broad Institute's Genomics Platform. Researchers hope the findings could lead to new drugs to help reduce the number of heart attacks in middle age. Dr Sekar Kathiresan, a cardiologist at Massachusetts General Hospital in Boston, said: ‘Our APOA5 result tells us beyond LDL levels - which are well known to contribute to heart attack risk - abnormalities in triglyceride metabolism also play an important role. ‘This gives us an important window into the biology of the disease and also suggests potential new avenues for therapeutic development.’ The study follows other recent genetic discoveries including the identification of protective mutations in the APOC3 gene, that lower ‘bad fat’ levels and the risk of heart attack. There are some striking parallels between this new study and similar work conducted over 40 years ago, which was led by Nobel Prize winner Professor Joseph Goldstein. His study examined several hundred people from Seattle who had suffered a heart attack before the age of 60. Looking at the levels of fats in the blood, his researchers identified high cholesterol levels as the major link. The study has bolstered previous studies that found that LDL - the major carrier of cholesterol in the bloodstream - causes atherosclerosis (illustrated using computer artwork), where fats accumulate in blood vessels and lead to a heart attack . That work spurred decades of research trying to unravel the role of LDL - the major carrier of cholesterol in the bloodstream - in causing atherosclerosis, where fats accumulate in blood vessels and lead to a heart attack. Interestingly the second most common abnormality observed by Professor Goldstein and his colleagues was elevated blood triglycerides, but he was unable to explain this comprehensively at the time. Dr Kathiresan and his colleagues also found harmful LDL receptor mutations are roughly twice as common than had been estimated in the Goldstein study. He said: ‘In 1973 Goldstein’s work taught us what types of lipids in the blood are most important for early heart attack risk. Now after sequencing all of the genes in the genome we can directly point to the specific genes that are most important. There is remarkable consistency between the observations from 40 years ago and today.’ Only about five per cent of people who suffer a heart attack do so at a relatively young age. But tragically the first sign of illness in this minority is often a devastating heart attack inflicting significant damage to the heart and resulting in severe disability or even death. There are 230,000 heart attacks in the UK every year - with about one-in-ten proving fatal.
Rare gene mutations that increase the risk of a attack if they have a faulty gene called APOA5. from the Broad Institute, Massachusetts General heart attack early in life. Those that had the risk. Scientists from the Broad Institute, a cardiologist at Massachusetts General Hospital Looking at the levels of fats in the blood, his about five per cent of people who suffer a heart tragically the first sign of illness in this minority is often a devastating heart attack