Updated on June 15, 2022
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WEDNESDAY, July 17, 2002 (HealthDayNews) -- Researchers have identified a genetic variant that helps protect against heart attack and stroke.
The variant could be used not only in a screening test but also as the basis for a new kind of protective cardiovascular therapy, says Dr. David Schwartz.
Schwartz is director of the center for environmental genetics at Duke University Medical Center and leader of the group reporting the finding in tomorrow's issue of The New England Journal of Medicine.
It's not the kind of genetic trait most people would associate with cardiovascular disease, since it's a form of a gene involved with the immune system's defenses against infection. However, its identification adds to a growing body of evidence that inflammation, including that caused when the body fights an infection, plays a major role in heart attack and stroke.
The idea is that molecules and cells that attack bacteria and viruses also attack the delicate tissue that lines the arteries, inflaming it and stimulating atherosclerosis -- the formation of plaque, the clotty deposits that eventually can block an artery and cause a heart attack or stroke.
There was enough evidence of that connection for Schwartz and his colleagues to zero in on genes that produce a family of proteins called "Toll-like receptors," which are found of the surface of immune system cells and also on the cells lining airways and blood vessels. These receptors recognize a specific lipid -- or fat -- on the surface of bacteria and signal the immune system that an invader is present.
One gene for one Toll-like receptor, called TLR4, has a variant that lessens the immune system's production of inflammatory cells and molecules, Schwartz says. The Duke researchers set out to learn whether this reduction decreased atherosclerosis.
They turned to Austria, where researchers have been following 810 patients since 1990, gathering detailed information on their immunological status and taking ultrasound pictures of the major arteries of the neck.
"They sent us the blood and we looked specifically for the presence of this polymorphism [gene variant]," Schwartz says.
The genetic studies from Austria showed that 55 of the 810 participants had the TLR4 gene. Blood tests showed those individuals had lower levels of inflammatory immune cells and molecules. And the ultrasound pictures showed the same 55 with the TLR4 gene had significantly less atherosclerosis.
"There are two potential ways, and possibly a third, to use this information," Schwartz says. "First, it could be used to screen individuals to see whether they are protected against atherosclerosis."
"Second, it is a novel mechanism that one could manipulate in a variety of different ways to affect the risk of developing atherosclerosis. Third, by identifying a mechanism that causes atherosclerosis, it opens the possibility of combination therapy, such as treating high cholesterol levels in conjunction with altering the activity of the receptor," he adds.
Screening would not be difficult, Schwartz says, because "given what we have reported, many laboratories could do it." Someone found to carry the TLR4 would be in luck, since "this particular factor appears to have about a 50 percent protective effect against the risk of atherosclerosis," Schwartz says.
Treatment might be possible because "there are specific agents that bind to the receptor and prevent its activity," he says. The trick would be to reduce the inflammatory damage without weakening immune defenses.
"We are in the process of identifying other genes that are potentially involved in this effect, and also in the process of considering human trials," Schwartz says.
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