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Six New Genes Associated With Heart Attacks

Affymetrix, Inc. (Nasdaq:AFFX) announced that its GeneChip® genotyping technology played a part in the recently announced discoveries of six new genes associated with susceptibility to heart attacks. Scientists from the University of Lübeck, Germany, and Massachusetts General Hospital, USA together with European and American colleagues, conducted three separate studies. They have all been published in the renowned scientific magazine, Nature Genetics. Researchers from the European Cardiogenics Consortium were involved with each of the three publications.

The scientists leveraged the power of the Affymetrix® Genome-Wide Human SNP Array 6.0 and the GeneChip® Human Mapping 500K Array Set to conduct large-scale gene association studies focused on demystifying the risk of heart attacks. Both products were designed to meet the needs of researchers focused on elucidating the molecular mechanisms of diseases, such as cardiovascular disease.

According to the National Center for Health Statistics in the U.S., almost 1.3 million heart attacks occur in the country each year, and about 37 percent of people who experience a heart attack in a given year die from it. This makes coronary heart disease the leading cause of death in America.1

The results of these studies contribute significantly to an overall understanding of the susceptibility to heart attacks and add to an ever-increasing store of knowledge about the molecular mechanisms of heart disease.

The first of the three publications describes a study by Jeanette Erdmann, et al., in which 1 million genetic markers were evaluated in 1,200 patients with heart attacks using the SNP Array 6.0.2 The study was replicated in a further 24,000 subjects. The authors identified two genetic loci on chromosomes 3 and 12 which they say were causally related to heart attacks. The MRAS gene on chromosome 3 is thought to play a role in the biology of blood vessels, while the HNF1A gene on chromosome 12 is likely involved in cholesterol metabolism. Both genes offer new avenues of investigation for scientists interested in the underlying mechanisms of coronary heart disease (CHD).

"We started using Affymetrix 500K Arrays in 2006 because the content of the arrays was unique. In 2007, we identified seven new loci for myocardial infarction,3, 4 largely as a result of early access to these arrays for our Cardiogenics Consortium," said Jeanette Erdmann, PhD, chief of the molecular genetic laboratory at the Department of Cardiology of the University of Lübeck and member of the Cardiogenics Consortium. "For our more recent study, we used the SNP Array 6.0 because of our very good experience with the 500K Array and we were very pleased with the results."

The second publication, by David Trégouët, MD, et al., used the 500K Array Set. The authors studied combinations of 4 genetic markers located in close proximity on the chromosomes in relation to the risk of experiencing a heart attack.5 With this approach, the authors identified a new gene, LPA, on chromosome 6 that was associated with heart attack risk. The LPA gene regulates the concentration of a certain lipoprotein, a particle which transports fatty acids, such as the lipoprotein (a), in the blood.

The 500K Array Set was the first product that enabled researchers to search across the entire genome to find genes involved in disease or drug response.6 In today's study by David Tregouet et al, scientists say they have illustrated the utility of genome-wide haplotype association analysis of genotype data using the 500K Array Set to identify new susceptibility loci for complex human diseases.

The final study, led by Sekar Kathiresan, MD and the Myocardial Infarction Genetics Consortium, leveraged the SNP Array 6.0 and the 500K Array Set to conduct gene association studies of early onset myocardial infarction, and identified genes on chromosomes 2, 6 and 21 that correlated with heart attacks.7 The results were verified by replication study of more than 19,000 samples. The authors confirmed five previous reports, bringing the total number of verified genetic loci for heart attack risk to nine. Using these nine markers, the authors were able to identify 20% of the population at more than two-fold increased risk for heart attack.

"We selected the Affymetrix SNP Array 6.0 because it provided us the ability to not only query SNPs but also common and rare copy number variants. Our study is the first to simultaneously study both SNPs and CNVs in the same sample for a common, complex trait," said Dr. Sekar Kathiresan, MD, Director, Preventive Cardiology at Massachusetts General Hospital and Assistant Professor of Medicine at Harvard Medical School.

The SNP Array 6.0 provides more than 946,000 probes for the detection of copy number variation (CNV) and more than 906,000 single nucleotide polymorphisms (SNP).8