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Gene linked to increased heart attack risk

9 February 2004
By BioNews
Appeared in BioNews 244

Icelandic, UK and US scientists have identified gene variants that double the risk of both heart attack and stroke. The team, lead by scientists at the Reykjavik-based firm deCODE Genetics, found that two versions of a gene called ALOX5AP are linked to an increased risk of both conditions. One version doubles the risk of heart attack and stroke in Icelandic people, whereas the other is associated with an increased risk in the UK population. It is not surprising that heart attacks should be linked to many genetic variations that have different frequencies in different populations, say the study authors, who published their findings in the journal Nature Genetics.

It has long been known that people with a family history of coronary artery disease are at increased risk of having a heart attack, although factors such as diet, diabetes and smoking also play an important role. Heart attacks and strokes are both associated with atherosclerosis (a build-up of fatty deposits that cause thickening of the artery walls), a condition which increases the risk of blood clots blocking the arteries that supply the heart or brain.

The ALOX5AP gene makes a protein called 5-lipoxygenase activating protein (FLAP), which is involved in making substances that trigger inflammation in the body. Research suggests that inflammation, the body's response to injury, may play an important role in triggering heart attacks and strokes, since blood clotting forms part of this response. Earlier this year, US researchers reported that variations in the ALOX5 gene, which makes another protein involved in inflammation, are also linked to an increased risk of heart attacks and strokes.

In the latest study, the scientists studied 296 Icelandic families, with a total of 700 members who had suffered a heart attack. They found that 29 per cent of the patients had inherited a particular version of ALOX5AP, which suggests that it confers a two-fold increased risk of the disease. Iceland is thought to have a genetically-distinct population, which is partly why deCODE decided to set up a national genetic database to track down disease genes. But critics of its approach have said that common genetic variations linked to illnesses in Icelanders may be rare in other populations. The variant form of ALOX5AP linked to heart attack in Icelandic patients was not associated with an increased risk of the condition in 750 British heart attack patients. However, the researchers found that compared to healthy people, UK heart attack patients were more likely to have inherited a different variation of the ALOX5AP gene. This version also appeared to double the risk of heart attacks and stroke, said the team.

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Nature |  8 February 2004
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