The researchers' findings are the first to demonstrate a strong connection between common variations in IL-1 genes and the production of CRP and other inflammatory proteins by the liver.
Numerous studies have identified inflammation as a major component of the atherosclerosis disease process, the accumulation of fatty plaques in arteries that can lead to heart attack or stroke. CRP, a protein marker of inflammation, has recently been recognized as a significant factor in understanding cardiovascular disease. IL-1, a primary regulator of inflammation, wound healing and bone and connective tissue responses following injury or the onset of disease, starts the chain reaction of inflammatory proteins that leads to production of CRP.
"By understanding the genetic underpinnings of cardiovascular disease, physicians may in the future be able to take a more complete approach to managing patient care," says Peter Berger, M.D., Mayo Clinic cardiologist and the lead author on the paper. "Factors that influence genetic predisposition to disease may enable doctors to identify patients who are most at risk at an earlier age. Furthermore, the growing body of knowledge about markers, such as CRP, may help physicians in monitoring the onset and progression of disease as well as the effectiveness of therapeutic interventions."
To evaluate genetic influence on the inflammatory response, researchers identified the presence of four common polymorphisms in IL-1 genes in 454 patients undergoing coronary angiography. Those variations were analyzed to determine their influence on plasma CRP and fibrinogen levels. CRP levels remained significantly associated with IL-1 polymorphisms after adjustment for smoking, gender and age. Levels of fibrinogen, another marker, had similar associations with the IL-1 genotypes.
The study was done in cooperation with researchers from Interleukin Genetics and University of Sheffield (England) and was funded by Interleukin Genetics.