Researchers Link Common Gene Variations to Levels of Biomarker for Cardiovascular Disease, C-Reactive Protein

Business Wire, May 17, 2002

Business Editors & Health/Medical Writers

WALTHAM, Mass.--(BW HealthWire)--May 17, 2002

Genetic Predisposition to Exuberant Inflammatory Response

May Complement CRP as Early Risk Factor for Cardiovascular

and Other Inflammatory Diseases

Interleukin Genetics, Inc. (NASDAQ:ILGN) and researchers at the Mayo Clinic announced today findings from a clinical study linking common genetic variations in the Interleukin-1 (IL-1) gene to levels of an important risk factor for complications due to cardiovascular disease, C-reactive Protein or CRP.

The researchers' findings, published in today's issue of the journal, Cytokine, are the first to demonstrate a strong connection between common IL-1 gene variations and the blood levels of CRP and other inflammatory proteins produced by the liver. These biomarkers have recently been reported to identify individuals who may be at greater risk for cardiovascular disease and other inflammatory disorders. Because the genetic variations are present from birth onward, testing for the presence of IL-1 SNP's (single nucleotide polymorphisms) and SNP combinations (haplotypes) may provide early prediction of a life-long susceptibility to chronic inflammatory disease, thereby enabling the identification of individuals who may benefit from prevention or early therapeutic intervention. For individuals at high risk of excessive inflammatory responses, regular monitoring of CRP and other protein markers may provide an indication of how well that inflammatory tendency is being controlled.

Numerous studies have identified inflammation as a major component of cardiovascular disease complications, such as myocardial infarction (heart attacks). CRP is a protein marker of inflammation that has recently joined the ranks of high cholesterol and smoking as significant factors in understanding risk for cardiovascular disease. CRP is produced in response to a cascade of inflammatory proteins, starting with IL-1, a primary regulator of inflammation, wound healing, and bone and connective tissue responses following injury or the onset of disease.

"Although substantial data indicate elevated CRP levels increase the risk of coronary events, there are limited explanations as to why some individuals without an apparent cause have elevated levels," stated Peter Berger, M.D., Division of Cardiovascular Diseases at the Mayo Clinic and lead author on the paper. "These data are the first to indicate that common IL-1 gene variations significantly influence the degree of systemic inflammation, as reflected by CRP and fibrinogen levels."

Study Design and Results

To determine the influence of the genetic control of the inflammatory response on the variability in levels of key protein markers of systemic inflammation, researchers genotyped 504 patients undergoing coronary angiography. The IL-1 genes that are known to modulate inflammation and the frequency of four common polymorphisms (SNPs) were analyzed to determine their influence on plasma C-reactive protein (CRP) and fibrinogen levels. Researchers found that CRP levels remained significantly associated with IL-1 polymorphisms after adjustment for smoking, gender and age. Fibrinogen levels had similar associations with the IL-1 genotypes.

The study was reported in a paper titled, "C-Reactive Protein Levels Are Influenced by Common IL-1 Gene Variations", published in the May 17, 2002 issue of the journal, Cytokine 2002; 17, 171-174, which was authored by Dr. Berger and his colleagues at the Mayo Clinic, together with investigators at Interleukin Genetics and the University of Sheffield in the UK.

As Dr. Ken Kornman, Interleukin Genetics' Chief Scientific Officer and an author on the paper explained, "These findings strongly support our approach to prolonging human health through understanding the biology of inflammation. We plan to combine this study information with the results from other studies in our TARxGET CVD program to produce and commercialize tools for the improved diagnosis, treatment and monitoring of patients with cardiovascular disease."

About Interleukin Genetics' TARxGET CVD Program

This study is one of several clinical and applied research studies that Interleukin Genetics is conducting to examine the role inflammation and genetic variations play in risk for cardiovascular disease. This study with the Mayo Clinic and the University of Sheffield is part of Interleukin Genetics' TARxGET program (Translating Advanced Research in Genomics into more Effective Therapeutics) for cardiovascular disease. Interleukin currently has three additional clinical studies underway.

Note to editors: For a reprint of the Cytokine paper or to speak with Dr. Berger from the Mayo Clinic, please call one of the company contacts listed below.

About Interleukin

Interleukin Genetics is a biotechnology company focused on inflammation. The company uses functional genomics to develop diagnostic and therapeutic products based on the genetic variations in people to help prevent or treat diseases of inflammation. Interleukin's TARxGET (Translating Advanced Research in Genomics into more Effective Therapeutics) programs focus on the areas of cardiovascular disease, rheumatoid arthritis and osteoporosis and include the development of tests to assess a person's risk for heart disease and osteoporosis as well as a test to help doctors and patients choose the best course of therapy for rheumatoid arthritis. These products will enable the managed care industry to improve patient care and better allocate resources. In addition to its research partnerships with numerous academic centers in the U.S. and Europe, Interleukin's corporate collaborators include the leading healthcare organizations, Kaiser Permanente and United Health Group. For more information about Interleukin and its ongoing programs, please visit http://www.ilgenetics.com