Genetic variant reduces immune response, yet protects against atherosclerosis

DURHAM, N.C. -- An international team led by Duke University Medical Center researchers has discovered that a genetic variant of an immune system receptor appears to simultaneously dampen the body's immune response to bacteria and other microbial toxins and to provide some protection against atherosclerosis, or clogging of the arteries. The scientists believe their discovery suggests a possible new approach to anti-atherosclerosis drugs.

The genetic variant, or polymorphism, occurs in one of a family of 10 receptors known collectively as "Toll-like receptors" (TLRs), reflecting the fact that the human receptors resemble Toll receptors first discovered in flies. These TLRs -- which are located on the surface of immune cells, heart muscle cells, airway epithelial cells and cells lining blood vessels -- are crucial to immune responses to bacteria. They recognize a specific lipid on the surface of bacteria and provide the first warning to the immune system that an invader is present. The researchers estimate that the polymorphism of the Toll-like receptor 4 (TLR4) they studied occurs in about 10 percent of the population.

"This particular polymorphism appears to attenuate the receptor signaling ability and to diminish the inflammatory response. Our results suggest that the diminished inflammatory response is responsible for a decreased risk of atherosclerosis," said Duke's David Schwartz, M.D., principal investigator for the study, the results of which were published today (July 18, 2002) in the New England Journal of Medicine. "We were quite encouraged that the data were so compelling in the degree to which this polymorphism is so protective.

"This represents a completely new mechanism involved in atherosclerosis and cardiovascular disease, and it provides a potential novel target for decreasing one's chances of developing heart disease," Schwartz continued. "In addition to using traditional means to reduce the risk of heart disease, such as ex

Contact: Richard Merritt
Duke University Medical Center

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