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Gene and diet clues to heart attack risk

8 January 2004
By BioNews
Appeared in BioNews 240

US researchers have identified a common gene variation that can increase the risk of heart attack and stroke - but only in combination with a diet high in certain types of fat. The new study, published in the New England Journal of Medicine, shows that people who inherit an altered version of a gene called ALOX5 are more at risk of the artery 'thickening' that can lead to heart attacks and strokes. The increased risk was highest in people who ate a lot of omega 6 (n-6) fatty acids whilst a diet high in omega 3 (n-3) fatty acids appeared to cancel out the genetic influence.

Teams at the Keck School of Medicine and the David Geffen School of Medicine, both in Los Angeles, studied 470 healthy, middle-aged men and women. The researchers looked at their ALOX5 gene type, measured their artery wall thickness, and recorded their dietary intake of omega 6 and omega 3 fatty acids. The former are found in sunflower, corn and other vegetable oils, while oily fish, rapeseed and other seed oils are rich sources of the latter.

The scientists found that people with variant forms of ALOX5, rather than the common form, were more likely to develop thickening of the artery walls (atherosclerosis). Thicker artery walls lead to narrower arteries, which increase the risk of heart attacks and strokes, as both are caused by blood clots. The ALOX5 gene makes a protein called 5-lipoxygenase, which in the body turns fatty acids into substances that trigger inflammation. Since atherosclerosis involves inflammation of the arteries, variations in the ALOX5 gene - especially those that affect the amount of 5-lipoxygenase produced in the body - could influence this process.

However, it seems that even people with a 'high-risk' variety of the ALOX5 gene could reduce their risk by eating plenty of the right sort of fatty acids: 'The adverse effect of this gene is increased by dietary intake of certain n-6 polyunsaturated fats, while the adverse effect is blocked by intake of fish oils containing n-3 polyunsaturated fatty acids', said study author James Dwyer. Several other studies have linked increased fish oil consumption with a reduced risk of heart attack.

The scientists say their results could lead to new treatments for atherosclerosis, as well as improved diagnosis and prevention of the condition. It has long been known that a 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. Another US study, reported at the end of last year, found that an alteration in a gene called MEF2A appeared to trigger heart attacks in several members of a single, large family. The latest study shows that as well as such rare gene mutations, common genetic variations can also influence the risk of heart attacks.

SOURCES & REFERENCES
Arachidonate 5-Lipoxygenase promoter genotype, dietary arachidonic acid, and atherosclerosis
New England Journal of Medicine |  2004
First link found in humans between common gene and artery-clogging disease
ScienceDaily |  2004
Gene 'raises heart attack risk'
BBC News Online |  4 January 2004
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