Presentations At AHA Expand On Clinical Utility Of DeCODE's DNA-based Tests

Main Category: Genetics
Also Included In: Cardiovascular / Cardiology;  Stroke
Article Date: 10 Nov 2008 - 2:00 PST

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Several presentations by deCODE genetics (Nasdaq:DCGN) scientists and independent researchers at the American Heart Association Scientific Sessions 2008 being held at the New Orleans Convention Center from November 8 to12 are expected to expand upon the clinical utility of evaluating individual risk of heart attack, or atrial fibrillation and stroke, respectively, by measuring the genetic markers that are the basis of the deCODE MI™ and deCODE AF™ tests. These tests measure single-letter variations in the human genome (SNPs) on chromosomes 9p21 and 4q25 that deCODE has linked to increased risk of these cardiovascular conditions, enabling a better understanding of individual risk. As this information is independent of other conventional risk factors, these tests provide doctors in the clinic with a new tool for improving screening, prevention and treatment.

Important avenues for expanding the clinical utility of the deCODE tests to be discussed at the AHA meeting are summarized below. To assist those interested in learning more about deCODE's tests while onsite at AHA or to follow proceedings on the AHA Web site, http://www.americanheart.org, deCODE would like to note below the titles, time, date and locations listed.

Myocardial infarction and 9p21 risk variants:

Several presentations focus on the 9p21 genetic risk markers for myocardial infarction (MI) that deCODE first reported in 2007 and which form the basis of the deCODE MI™ test for assessing individual risk as an aid in clinical practice. Individuals who have the at-risk versions of the SNPs detected by this test are 1.6- to 2-fold more likely to develop MI than are those with lowest risk genotypes, or at 1.3- to 1.5-fold higher risk than the general population. This level of risk is comparable to the risk due to highest quintile LDL cholesterol and is as common, with about 25 percent of the general population carrying the high-risk markers.

In the Sunday morning session, deCODE reviewed the latest findings on these 9p21 variants in MI and other cardiovascular conditions for which these SNPs are risk factors, including abdominal aortic aneurysm and intracranial aneurysm. The session also summarized the results of a UK clinical study showing that the accuracy of MI risk prediction is increased by measuring these 9p21 variants in addition to conventional risk factors. In two Tuesday sessions, Christie M. Ballantyne, M.D., and his colleagues from Baylor College of Medicine will discuss the clinical utility of measuring the 9p21 markers in addition to conventional risk factors for MI in the context of the ARIC study.

The 4q25 variants and risk of atrial fibrillation and stroke In 2007, deCODE discovered two SNPs on chromosome 4q25 that double the risk of atrial fibrillation (AF), and launched its deCODE AF™ test to detect these variants. Given that AF is underdiagnosed, one principal purpose of this test is to enable the identification of people at higher risk and to monitor them more intensively and to put those who exhibit AF on appropriate medication.

At this year's AHA, deCODE and independent groups will present data from studies that expand the understanding of how deCODE AF can contribute to better clinical practice. deCODE's original discovery of the 4q25 SNPs was replicated and validated in several European and U.S. case-control cohorts. Since then, the company has published findings that the SNPs in deCODE AF also confer risk of ischemic stroke, with highest risk for cardioembolic stroke. At AHA the company will discuss the implications of linking these markers not only with risk of AF, but also to risk of stroke and non-cardiogenic stroke. One implication is that AF appears to cause an even larger proportion of stroke than originally thought. This strengthens the case for going beyond standard cardiac monitoring, for hospitalized and discharged patients who have suffered stroke or transient ischemic attack (TIA), and for the prescription of warfarin, rather than Plavix™ or aspirin, for those with AF. deCODE will also present data on the utility of deCODE AF™ for detecting recurrent AF.

Researchers from Cleveland Clinic have conducted their own study of the link between the 4q25 markers and AF, and will look at correlations between these variants and mRNA expression profiles of the nearby PITX2 gene, which is expressed in atrial cardiac muscle. Groups from Brigham and Women's Hospital and Vanderbilt University examine the utility of testing for these variants to predict likelihood of developing AF after cardiac surgery, a complication that is associated with increased morbidity and mortality. Determining which patients may most benefit from prevention therapy with anti-arrhythmic medications is important because these drugs have side effects that make them unsuitable for use in all patients.

Among the talks relevant to the utility of deCODE MI™ and deCODE AF™ are those listed below.

Sunday, November 9

• 9:00-9:20am, Room 267-268, presentation number 275, "Genetics of coronary heart disease and risk factors." Presenter: Kari Stefansson, deCODE genetics.
  
  
• 4:15-4:30pm, Room 225-227, presentation number 1171, "Risk variants for atrial fibrillation on chromosome 4q35 associate with non-cardiogenic stroke, suggesting that AF is a much greater cause of stroke than previously recognized." Presenter: Jeff Gulcher, deCODE genetics.

Tuesday, November 11

• 9:30-9:45am, Room 355, presentation number 4985, "Are all patients considered 'low risk' for coronary heart disease really low risk? An analysis from the Atherosclerosis Risk in Communities (ARIC) study." Presenter: C.M. Ballantyne, Baylor College of Medicine
  
  
• 10:45-11:00am, Room 265-266, presentation number 4403, "Significant single nucleotide polymorphism associated with atrial fibrillation located on chromosome 4q25 in a whole genome association study and association with left atrial gene expression." Presenter: Mina Chung, Cleveland Clinic.
  
  
• 11:00-11:15am, Room 265-266, presentation number 4404, "Variation in the 4q25 chromosomal locus predicts new-onset atrial fibrillation after cardiac surgery." Presenter: Simon Brody, Brigham and Women's Hospital.
  
  
• 11:15-11:30am, Room 265-266, presentation number 4405, "Sequence variant for atrial fibrillation on chromosome 4q25 near the PITX2 gene increases risk for recurrent AF." Jeffrey Gulcher, deCODE genetics.
  
  
• 2:30-2:45pm, room 350-351, presentation number 5090, "Impact of adding a single allele in the 9p21 locus to traditional risk factors on risk classification for coronary heart disease and implications for lipid-modifying therapy in the white population of the Atherosclerosis Risk in Communities (ARIC) study." Presenter: C. M. Ballantyne, Baylor College of Medicine.

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About deCODE

deCODE is a bio-pharmaceutical company developing drugs and DNA-based tests to improve the treatment, diagnosis and prevention of common diseases. Its lead therapeutic programs, which leverage the company's expertise in chemistry and structural biology, include DG041, an antiplatelet compound being developed for the prevention of arterial thrombosis; DG051 and DG031, compounds targeting the leukotriene pathway for the prevention of heart attack; and DG071 and a platform for other PDE4 modulators with therapeutic applications in Alzheimer's disease and other conditions. deCODE is a global leader in human genetics, and has identified key variations in the genome (SNPs) conferring increased risk of major public health challenges from cardiovascular disease to cancer. Based upon these discoveries deCODE has brought to market a growing range of DNA-based tests for gauging risk and empowering prevention of common diseases. Through its CLIA-registered laboratory, deCODE is offers deCODE T2™ for type 2 diabetes; deCODE AF™ for atrial fibrillation and stroke; deCODE MI™ for heart attack; deCODE ProCa™ for prostate cancer; deCODE Glaucoma™ for a major type of glaucoma; and deCODE BreastCancer, for the common forms of breast cancer. deCODE is delivering on the promise of the new genetics.SM Visit us on the web at www.decode.com; on our diagnostics site at www.decodediagnostics.com; for our pioneering personal genome analysis service, integrating the genetic variants included in these tests and those linked to another twenty common diseases, at http://www.decodeme.com; and on our blog at http://www.decodeyou.com.

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Contact: Amy Speak
deCODE genetics

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