Celera Diagnostics Identifies Novel Genetic Markers Linked to Increased Risk of Heart Attack; Discoveries Published in the American Journal of Human Genetics - Expanded Understanding of Disease Biology Creates Diagnostic Opportunities

Business Wire, August 29, 2005

ALAMEDA, Calif. -- Scientists from Celera Diagnostics today published novel findings linking genetic variations in four genes with an increased risk for myocardial infarction (MI), or heart attack. None of these gene variants have previously been associated with MI, and they could lead to the identification of new coronary heart disease (CHD) mechanisms. This paper will appear in the October 2005 edition of the American Journal of Human Genetics, and is currently available on the publication's website at www.ajhg.com. Celera Diagnostics, a joint venture between the Applied Biosystems Group (NYSE:ABI) and Celera Genomics Group (NYSE:CRA) of Applera Corporation, conducted the study in collaboration with researchers at Quest Diagnostics (NYSE:DGX), the Cleveland Clinic Foundation and the University of California, San Francisco.

These findings are the latest in a series of communications regarding MI and other cardiovascular disease-related discoveries made by Celera Diagnostics and its collaborators, as well as discoveries toward understanding the genetic basis for individuals who derive increased benefit from statin therapy in preventing MI. Celera Diagnostics has completed association studies in several cardiovascular diseases and the pharmacogenomics of treatment for cardiovascular diseases, and has additional studies with data from more than 30,000 subjects.

"This study, coupled with other prospective studies underway at Celera Diagnostics, is providing valuable insight toward the ongoing development of a 'Genetic Risk Score' that is expected to identify individuals at elevated risk for MI," said Kathy Ordonez, President of Celera Diagnostics. "More than 17 million people in the United States fall into the category of moderate risk for having a heart attack using existing methods of evaluation, such as measuring serum cholesterol, blood pressure, and assessing the genetic component through taking a family history. A 'Genetic Risk Score' will not only enable physicians to make a quantitative estimate of each individual's relative genetic risk for MI, but importantly it will also identify those individuals who would otherwise not have been considered at risk for MI, and who could benefit from preventive treatment."

"We are in the process of translating these findings into clinical practice and moving toward the commercialization of these exciting discoveries," Ms Ordonez added. "We continue to work closely with our clinical laboratory collaborators on prospective studies of the general population to identify the most informative constellation of diagnostic markers associated with MI and increased statin benefit, and anticipate communicating these as they are published over the coming months."

"Multiple large scale studies for discovery, with well-characterized DNA samples from carefully selected patients and matched controls, hold significant promise to discover new gene variants that predict risk for MI and will enable the development of new diagnostics," said Ray Fenwick, Ph.D., Scientific Director, Molecular Endocrinology at Quest Diagnostics Nichols Institute, and a co-author of the paper. "In addition, the replication of our results in two additional case-control studies confirms the significance of these results in identifying individuals at increased risk for heart attack even when standard risk factors such as smoking and obesity are taken into account."

Summary of Scientific Findings

Celera Diagnostics evaluated DNA samples from more than 3,000 individuals in three studies to compare patterns of genetic variation in people with a history of MI to those with no history of CHD. The results were replicated in all three studies.

This study found that variants in four genes were associated with MI in three studies. These gene variants encode the cytoskeletal protein palladin, a tyrosine kinase, and two G protein-coupled receptors. Each of these gene variants individually confers an increased risk for MI that is comparable to conventional risk factors such as smoking, high blood pressure and elevated cholesterol levels.

These genetic markers were identified through a genome-wide study of 11,053 single nucleotide polymorphisms (SNPs) in 6,891 genes of a broader scan, focusing on SNPs that could influence gene function in order to increase the likelihood of identifying disease-causing gene variants. To minimize false positive associations generated by multiple testing, two studies were used to identify a limited number of nominally associated SNPs; a third study tested the hypotheses that these SNPs are associated with MI.

About Myocardial Infarction

Commonly known as a heart attack, a myocardial infarction occurs when a coronary artery is blocked, restricting blood flow to the heart. MI is a multi-factorial disease associated with both environmental and genetic factors. Some of the major risk factors associated with MI include high cholesterol, high blood pressure, diabetes, smoking and obesity. Although major risk factors are associated with the majority of MI events, it is difficult to predict individual outcomes based on these risk factors, and many people do not have symptoms of coronary disease before their first MI. This year an estimated 700,000 Americans will experience their first coronary attack, according to the American Heart Association. Approximately 7.6 million people in the United States age 20 and older have survived a heart attack.