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Gene Tied to Heart Attack, Stroke Risk

11 May 2004 (All day)
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The difference between health and the hospital could be as slight as a one-letter difference in the DNA sequence that codes for a molecule involved in inflammation. One version of the gene appears to protect against heart attacks and stroke, a new study finds.

As we age, fat and blood cells form hard plaques on the walls of our arteries. If these plaques burst, clumps of fat spew into the bloodstream, potentially clogging arteries and triggering a heart attack or stroke. Recently, several lines of evidence have suggested that inflammation plays an important role in the process (ScienceNOW, 9 February). For example, researchers have found that immune cells living in plaques make prostaglandins, key players in inflammation that make the plaques more vulnerable to rupture.

Francesco Cipollone of the "G. d'Annunzio" University of Chieti, Italy, and colleagues wondered whether genetic variations in the gene for COX-2, an enzyme that stimulates prostaglandin production, might influence heart attack and stroke risk. To investigate, the team examined the COX-2 gene in 1700 people: half of whom had suffered a heart attack or stroke due to a plaque breach.

Previous work had shown that two variations in the COX-2 gene, with either a guanine (G) or a cytosine (C) molecule at a particular spot in the gene's DNA sequence, lead to different levels of COX-2 protein. In the current study, Cipollone's team found that people with two copies of the C version had a 67% lower risk for heart attack and stroke than did those with two copies of the G version. Tissue samples from arteries showed that plaques from people with two C versions had a lot less COX-2 protein than those from volunteers carrying two G versions, supporting the idea that less COX-2 translates to less inflammation and lower rupture risk, the team reports in the 12 May Journal of the American Medical Association. In addition to heart attack and stroke risk, Cipollone says that the two versions of the genes might account for the fact that some patients do not respond to COX-2 inhibitors, which are used to protect against plaque cracking.

"The study is interesting and provocative," says cardiologist Garret FitzGerald of the University of Pennsylvania Medical School in Philadelphia. But the number of participants is too small to conclusively say how much protection the C version of COX-2 confers. Additional research is also needed to determine how the C version of the gene affects the protein's function.

Related site
Cipollone's site

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