Genetics and stem cells

Genetic variation 'reduces risk of heart disease in women'

"Scientists have identified a gene that puts women at higher risk of heart disease, an early study suggests," BBC News incorrectly reports. But the study in question has not found a new gene: researchers found that a switch in one of the building blocks of DNA present in some women is associated with a reduced risk of cardiovascular disease (CVD).

There are just four building blocks that, in millions of combinations, make up DNA. Researchers found that if there is a switch in two of the building blocks – guanine and adenine – at a single point on chromosome 16, this may have a protective effect against CVD.

The evidence suggests this was most beneficial if both strands of the DNA had adenine. This switch has the catchy name of rs4888378, and is a single nucleotide polymorphism (SNP).

The researchers think the protective effect might be because SNP has an influence on how active a gene called BCAR1 is. This gene has many functions, one of which is to help cells stick together and replicate in the walls of blood vessels after injury.

This study found women with guanine in each SNP had higher BCAR1 activity. The researchers speculated that this may encourage the thickening of blood vessels seen in CVD, but this has not yet been proved. The study did not directly look at BCAR1 activity and CVD, or indeed any other variations of BCAR1 genes.

The BCAR1 gene is present in both men and women, and has many "healthy" functions. It is often reported in the media because certain genetic variations in this gene increase the risk of breast cancer. 

Where did the story come from?

The study was carried out by researchers from University College London, the Technical University of Denmark, the University of Milan, the University of Edinburgh, the University of Essex, Bassini Hospital, Karolinska University Hospital, and Lund University.

It was funded by the European Commission, and numerous government grants and charitable foundations across Europe.

The study was published in the peer-reviewed medical journal Circulation: Cardiovascular Genetics.

BBC News did not report the study accurately. The story says that, "women who had a particular version of the BCAR1 gene were more likely than other women to have heart attacks and strokes", but this was not the case. The study looked at changes in SNPs, not the BCAR1 genes.

But the BBC did provide helpful expert comments from the lead researcher, who put the results of the study into perspective by saying that the SNP gene and BCAR1 gene may be involved, but she "expect[s] there are a lot of other factors at play". 

What kind of research was this?

This research consisted of a combination of laboratory DNA analysis and a meta-analysis pooling results from five cohort studies.

CVD causes a quarter of all deaths in the UK, and there are an estimated 7 million people living with the disease. Known risk factors include:

  • high blood pressure
  • type 2 diabetes
  • smoking
  • high cholesterol
  • poor diet
  • lack of physical exercise
  • being overweight or obese

People often have no symptoms in the early stages of the disease. However, an ultrasound of the carotid arteries in the neck can show if CVD is developing if there is an increased thickness of the inner two layers of the artery.

The IMPROVE cohort study, which looked at more than 3,700 people with at least three of these risk factors, found an association between carotid artery thickness, CVD and an SNP on chromosome 16. People who had this type of SNP appeared to be protected against CVD.

This current study aimed to further investigate this SNP and the genes surrounding it. This type of study can find associations between SNPs, gene expression and risk of CVD, but cannot tell the whole story about how each risk factor combines or contributes to the development of the condition. 

What did the research involve?

The researchers performed DNA analysis on samples from the PLIC cohort study of more than 2,100 people from the general population of Italy. They wanted to see if the SNP was associated with carotid artery thickness.

The results were then combined in a meta-analysis with the original IMPROVE cohort and three others: the Whitehall II (WHII) study, the Edinburgh Artery Study, and the cardiovascular arm of the Malmö Diet and Cancer Study.

The researchers then analysed the genes around this SNP on chromosome 16, to see if any of them might have an effect on CVD risk. 

What were the basic results?

Overall, there was no association between the SNP and thickness of the carotid arteries at the beginning of the PLIC study or over six years of follow-up.

However, women who had adenine on both strands of the SNP had 20% slower thickening of the carotid arteries each year.

Even if the women only had adenine on one strand and guanine on the other, this still seemed to have a protective effect, slowing the rate by 10% a year, compared with women who had guanine on both strands. There was no effect for men.

A similar result was found when the researchers combined the results of the PLIC study with the other four cohort studies.

In further tests, it appeared the SNP might actually be "functional", and the different version may be having a direct effect on the development of CVD.

The researchers also found the BCAR1 gene was more active in people with guanine on both strands of the SNP. The BCAR1 gene is involved in many processes, including increasing cell division in the smooth muscle of blood vessels after injury.

As this gene activity was higher in people who had the guanine version of the SNP, the researchers suggested this may be important in the formation of plaques (clumps of fatty substances) in hardening of the arteries (atherosclerosis), which is part of the process of CVD. 

How did the researchers interpret the results?

The researchers concluded that: "This study has identified a potentially functional variant for the association of the chromosome 16 locus with CIMT [carotid intima-media thickness] and CVD risk using bioinformatics and functional assays."

They suggest an interaction between this SNP and increased activity of the BCAR1 gene and oestrogen may contribute to CVD in women, but larger studies are required to further understand the mechanisms and how big a role they play compared with other known risk factors. 


This laboratory study found that women with adenine on either strand of an SNP in a section of chromosome 16 have a lower risk of CVD, as evidenced by a slower increase in thickness of the carotid arteries over a six-year period.

These findings were replicated in the meta-analysis of all five cohort studies. No association was found for men.

Further laboratory studies found the gene called BCAR1 – which is located nearby on the same chromosome – is more active in women with guanine on both strands of the SNP.

BCAR1 is not a new gene – it is present in men and women, and has a variety of functions throughout the body. It is not yet known if this gene has a role in the development of CVD, but this will no doubt be a focus of future research.

Regardless of whether the risk of CVD is slightly higher or lower according to your genes, the most important thing you can do to reduce your risk of CVD is to stop smoking. Other modifiable risk factors are to take regular exercise, lose weight, have a healthy diet that includes plenty of fruit and vegetables, limit your alcohol intake, and reduce your blood pressure.

NHS Attribution