Kat Arney

Heart Disease gets in a FLAP

Iceland provides a fertile breeding-ground for genetic studies,

as the population is relatively isolated making it easy to find

genes involved in specific syndromes. The researchers pinned down

FLAP by looking for people who had suffered heart disease or stroke.

By comparing 700 heart patients with their unaffected relatives

they found a region of DNA on chromosome 13 which was common to

many of the patients. A further 1600 patients helped them to narrow

down the region, pinpointing the FLAP gene. They found that certain

versions of FLAP doubled the risk of both diseases in Icelandic

populations, while another FLAP variation doubles the likelihood

of a heart attack in British people. But what does FLAP do?

Initially, FLAP was fingered by scientists investigating asthma.

They found that the FLAP gene made a protein with a role in producing

leukotrienes, chemical signals secreted by cells in the immune system.

When someone has an asthma attack, immune cells in the lungs produce

leukotrienes which cause the airways to swell so air cannot get

in and out properly. Although they seem different, asthma and heart

disease are both ailments involving inflammation (swelling). Recent

research has shown that the artery-clogging disease atherosclerosis

involves inflammation of the blood vessels. When the wall of a blood

vessel is damaged, immune cells cluster at the site of the injury

and produce leukotrienes. These chemicals recruit more immune cells

which help to build up the fatty deposits which are typical of atherosclerosis

(see the figure below) and which progressively block the

artery. These diseased regions in blood vessels are prone to developing

blood clots (thrombi) which can block important blood arteries in

the heart, causing a heart attack, or break loose and lodge in the

brain, causing a stroke.

When the scientists investigated patients with the heart disease-prone

version of FLAP, they found that their cells made more of these

inflammatory leukotrienes than normal people. The researchers think

that these high levels of leukotrienes could predispose people to

developing atherosclerosis. Experiments by other researchers have

also shown a link between high levels of leukotrienes, overactive

FLAP, and atherosclerosis. The scientists in Iceland are now carrying

out a clinical trial to find out whether an anti-asthma drug, that

works by blocking the action of FLAP, can also have an effect on

atherosclerosis.

The discovery that FLAP, and the associated leukotrienes, may play

a role in the development of heart disease and strokes is very exciting.

The research points towards leukotrienes as being important targets

for new drugs designed to combat cardiovascular problems, either

by blocking the effects of leukotrienes on arteries, or by blocking

the production of these molecules. It also shows how important genetic

studies will become in assessing our risk of disease, for better

or for worse. Perhaps we will see the introduction of a test to

identify people with a dodgy FLAP gene, which will ensure they get

suitable preventative therapy. Lifestyle factors such as smoking

play a big part in heart disease, so those at increased risk could

be warned in advance to stay off the cigarettes, lose weight, eat

healthily, or take up sport. But such genetic screening technology

leaves people open to exploitation by health and life insurance

companies. Would people with risky FLAP genes be made to pay higher

premiums even though it is only a factor in heart disease and not

a sole cause? As we discover more about the hidden secrets in our

genes, and their links to disease, we will have to answer these

ethical questions as well as tackling the scientific ones.

- October 2004

About the Author

Kat Arney is a writer and member of the naked scientists radio programme. She is based at Cancer Research UK