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The BBC's Daniel Sandford
"The advise from doctors to all smokers is still give it up"
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Professor Steve Humphries, University College London
explains the results of his study
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Friday, 13 July, 2001, 07:10 GMT 08:10 UK
Gene linked to heart disease risk
Male smokers with the gene variant are at increased risk
Male smokers with the gene variant are at increased risk
Scientists have discovered a gene which increases smokers' risk of developing coronary heart disease by up to four times.

Around a quarter of the population carries one or more copies of the key gene variant.

But researchers say genetic tests to warn who is at risk will not be commercially available until further studies have confirmed their findings.

Smokers are known to have an increased risk of developing heart disease, because smoking increases the risk of blood clots and blocked arteries.

Men who carried the E4 type are at higher risk of heart disease, but only if they are smokers

Professor Steve Humphries, University College London
But this study may explain why some smokers get heart disease while others get lung cancer or bronchial problems.

And heart health experts say they hope the information will help motivate smokers to stop.

The gene which has been studied is Apo-E which produces a protein and helps control levels of fats in the blood. There are three variations, E2, E3 and E4.

E4 is the variant linked to highest risk.

Risk factors

Everyone has two copies of the gene, one from their mother and one from their father.

Professor Steve Humphries
Professor Steve Humphries warned against smoking
Scientists in this study found risk was increased just by having one E4 variant. They speculate people with two E4 copies would be at increased risk.

Researchers from University College London (UCL) and the Wolfson Institute at St Bartholomew's Hospital tracked the heart health of over 3,000 men aged between 50 and 61 over eight years.

All had checks to assess their cholesterol levels and other heart disease risk factors.

DNA techniques were used to identify which type of the gene the men had.

Current smokers had double the risk of having a heart problem than those who had never smoked.

But men who smoked and had the E4 variant had a three-fold risk compared to those who had never smoked, when the risk factor of the gene was considered on its own.

When taken along with other risk factors such as obesity, the increased risk was nearly four times as high.

But E4 variant smokers who quit see their risk reduced to roughly the levels of non-smokers, say the scientists.

E4 had previously been recognised as a risk factor for coronary heart disease. This research confirms the link and extends the findings to a younger age group.


Steve Humphries, British Heart Foundation professor of cardiovascular genetics at UCL, said: "Men who carried the E4 type are at higher risk of heart disease, but only if they are smokers".

Artery walls are damaged by chemicals from tobacco smoke which make holes in the wall lining, and damage LDL, the "bad" form of cholesterol.

The damaged LDL particles enter the holes and accumulate on the artery walls. That triggers an immune response in the body and attracts large numbers of white blood cells to the site.

That causes plaque to form, which can block the artery and lead to blood clots. Apo-E is thought to stop the damage being done to the cholesterol, but with varying degrees of effectiveness.

Professor Humphries said: "E2 is best at this, E3 is not so good, and E4 is downright terrible."

Professor George Miller of the Wolfson Institute, who also worked on the study, said: "There is no test widely available for this gene, and even if there were, doctors cannot treat you for having a gene."

Sir Charles George, medical director of the British Heart Foundation, said: "I hope the information gained in this study will help to motivate the many smokers who want to quit."

More studies will now be carried out, looking at the gene's effect on women, and seeing if this first study's results are replicated.

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