Affymetrix® Microarray Technologies Help Scientists Understand the Genetic Risk of Heart Attacks

SANTA CLARA, Calif.–Affymetrix, Inc. (Nasdaq:AFFX) today 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

“These scientific findings offer hope that someday soon we will be able to answer important questions that could lead to the earlier identification of individuals at risk of heart attack or disease,” said Kevin King, president and CEO of Affymetrix. “Helping our customers to more deeply understand the underlying basis of human genetic variation and disease is a major goal for our company and aligns well with our continued investments into next-generation genotyping technologies that are planned for later this year.”

1National Center for Health Statistics and NHLBI. National Health and Nutrition Examination Survey (NHASNES, 2006-06).

2Erdmann J., et al. New susceptibility locus for coronary artery disease on chromosome 3q22.3. Nature Genetics 41:280-282 (2009).

3Press Release: The Wellcome Trust Case Control and Cardiogenics Consortiums Identify Key Genes in Coronary Artery Disease with Affymetrix Technology.

https://investor.affymetrix.com/phoenix.zhtml?c=116408&p=irol-newsArticle&ID=1027940&highlight=

4Samani N. J., et al. Genome-wide Association Analysis of Coronary Artery Disease. New England Journal of Medicine 357(5):443-53 (2007).

5Tregouet D.-A., et al. Genome-wide haplotype association study identifies the SLC22A3-LPAL2-LPA gene cluster as a risk locus for coronary artery disease. Nature Genetics 41:283-285 (2009).

6Press Release: New Affymetrix Microarray Set Genotypes More Than 500,000 SNPs in a Single Experiment.

https://investor.affymetrix.com/phoenix.zhtml?c=116408&p=irol-newsArticle&ID=761893&highlight

7Myocardial Infarction Genetics Consortium. Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants. Nature Genetics 41:334-341 (2009).

8Press Release: Affymetrix Sets New Standard in Genotyping With Genome-Wide Human SNP Array 6.0.

https://investor.affymetrix.com/phoenix.zhtml?c=116408&p=irol-newsArticle&ID=1004567&highlight

About Affymetrix

Affymetrix provides industry-leading technologies to support the analysis of complex genetic and genomic information, particularly in the context of research studies focused on elucidating the molecular mechanisms of disease and drug response. After inventing microarray technology in the late 1980s, Affymetrix has been dedicated to developing innovative new products that provide researchers with a more complete view of the genome.

Today, Affymetrix technology is used by the world’s top pharmaceutical, biotechnology, and diagnostic companies, as well as leading academic, government, and non-profit institutes. More than 1,800 systems have been shipped around the world, and more than 17,000 peer-reviewed papers have been published using the technologies.

Affymetrix is headquartered in Santa Clara, Calif. The company has about 1,100 employees worldwide and maintains manufacturing, sales, and distribution operations across America, Europe, and Asia. For more information, please visit www.affymetrix.com.

Forward-looking Statements

All statements in this press release that are not historical are “forward-looking statements” within the meaning of Section 21E of the Securities Exchange Act as amended, including statements regarding Affymetrix’ “expectations,” “beliefs,” “hopes,” “intentions,” “strategies” or the like. Such statements are subject to risks and uncertainties that could cause actual results to differ materially for Affymetrix from those projected, including, but not limited to: risks and uncertainties relating to commercial success of the agreement with Cardiogenics Consortium discussed in this press release; risks of the company’s ability to achieve and sustain higher levels of revenue, higher gross margins and reduced operating expenses; uncertainties related to technological approaches, manufacturing and product development; personnel retention; uncertainties related to cost and pricing of Affymetrix products; dependence on collaborative partners; uncertainties related to sole-source suppliers; risks associated with past and future acquisitions; uncertainties relating to FDA and other regulatory approvals; competition; risks relating to intellectual property of others and the uncertainties of patent protection and litigation. These and other risk factors are discussed in Affymetrix’ Form 10-K for the year ended December 31, 2008, and other SEC reports, including its Quarterly Reports on Form 10-Q for subsequent quarterly periods. Affymetrix expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in Affymetrix’ expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based.

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