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Celera Identifies FCAR Genetic Polymorphism Associated with Increased Risk for Myocardial Infarction.


Individuals With FCAR FCAR Full Size Car
FCAR First Carolina Investors, Inc. (stock symbol)
FCAR Florida Coalition for Assessment Reform
FCAR Forwarding Chain and Aggregate Reservation
 Genetic Polymorphism Derive Better Than Average Protection from Statin Therapy

Study Confirms Genetic Basis for Individuals at Elevated Risk for Heart Attack Who Derive Better Than Average Protective Benefits of Statin Treatment

ROCKVILLE, Md. -- Celera Genomics (NYSE NYSE

See: New York Stock Exchange
:CRA See Community Reinvestment Act. ), an Applera Corporation business, today announced a publication describing a genetic polymorphism in the gene encoding the myeloid myeloid /my·eloid/ (mi´e-loid)
1. medullary; pertaining to, derived from, or resembling bone marrow or the spinal cord.

2. having the appearance of myelocytes, but not derived from bone marrow.
 IgA Fc receptor, the FCAR Asp92Asn polymorphism, associated with increased risk for myocardial infarction (MI) and coronary heart disease coronary heart disease: see coronary artery disease.
coronary heart disease
 or ischemic heart disease

Progressive reduction of blood supply to the heart muscle due to narrowing or blocking of a coronary artery (see atherosclerosis).
 (CHD CHD coronary heart disease.

ChD
abbr.
Latin Chirurgiae Doctor (Doctor of Surgery)


CHD,
n.pr See disease, coronary heart.


CHD

canine hip dysplasia.
). These results were obtained in genetic studies of two separate prospective randomized clinical trials assessing the effect of pravastatin pravastatin /prav·a·stat·in/ (prav´ah-stat?in) an antihyperlipidemic agent that acts by inhibiting cholesterol synthesis, used as the sodium salt in the treatment of hypercholesterolemia and other forms of dyslipidemia and to lower the  on prevention of MI and CHD: the Cholesterol and Recurrent Events study (CARE) and West of Scotland
  • West of Scotland is one of the eight electoral areas for the Scottish Parliament through which 7 of the 56 Additional Members System MSPs are elected.
  • West of Scotland Rugby Football Club
  • West of Scotland Cricket Club
 Coronary Prevention Study (WOSCOPS WOSCOPS  Cardiology A trial–West of Scotland Coronary Prevention Study–of the effect of pravastatin on M&M–risk of CHD, malignancy and other outcome data–in men with hypercholesterolemia. See Lipid-lowering therapy, Pravastatin. ). The risk of coronary events associated with the FCAR Asp92Asn polymorphism in both CARE and WOSCOPS was independent of other known risk factors. Further, the publication also reported that the increased risk of MI and CHD associated with this polymorphism could be significantly reduced in individuals that were treated with pravastatin, a lipid-lowering compound with anti-inflammatory properties. This paper will appear in the December 2006 edition of Arteriosclerosis arteriosclerosis (ärtĭr'ēōsklərō`sis), general term for a condition characterized by thickening, hardening, and loss of elasticity of the walls of the blood vessels. , Thrombosis and Vascular Biology, and is currently available on the publication's website at http://atvb.ahajournals.org/.

The CARE study was led by Frank M. Sacks, M.D., Professor of Cardiovascular Disease Prevention, Harvard School of Public Health The Harvard School of Public Health is (colloquially, HSPH) is one of the professional graduate schools of Harvard University. Located in Longwood Area of the Boston, Massachusetts neighborhood of Mission Hill, next to Harvard Medical School and Cambridge, Massachusetts,  and Harvard Medical School Harvard Medical School (HMS) is one of the graduate schools of Harvard University. It is a prestigious American medical school located in the Longwood Medical Area of the Mission Hill neighborhood of Boston, Massachusetts. . The WOSCOPS study was led by Professor James Shepherd, Department of Biochemistry, University of Glasgow The University of Glasgow (Scottish Gaelic: Oilthigh Ghlaschu, Latin: Universitas Glasguensis) was founded in 1451, in Glasgow, Scotland.  and Royal Infirmary.

"This study is among the first to describe genetic polymorphisms that could identify individuals who are not only at greater risk for coronary heart disease and heart attacks, but who also derive significant benefit from preventative statin treatment," said Dr. Sacks. "This genetic information increases accuracy of identifying people who are at high risk of heart attacks, and whose risk can be lowered by statin therapy. Our findings also suggest a new link between the immune system and cardiovascular disease."

The genetic association studies were performed with samples from the male subjects of the CARE trial (2,523 men) and with samples from the all-male WOSCOPS trial (1,562 participants in a nested case control study). The subjects carrying the 92Asn allele allele (əlēl`): see genetics.
allele

Any one of two or more alternative forms of a gene that may occur alternatively at a given site on a chromosome.
 in the FCAR gene had 68% higher incidence of MI in CARE and 49% higher risk of CHD in WOSCOPS compared to noncarriers. This genetic information appears to complement traditional risk factors because these risk levels remained similar after adjustment for traditional risk factors including subject's age, baseline LDL-C LDL-C low-density-lipoprotein cholesterol  ("bad" cholesterol) levels, baseline HDL-C HDL-C high-density-lipoprotein cholesterol.  ("good" cholesterol) levels, and history of smoking, hypertension, and diabetes. The risk estimates for the FCAR polymorphism were similar in magnitude to risk estimates for smoking. Pravastatin treatment reduced the absolute risk in carriers of the FCAR risk allele by 10% and 4% in CARE and WOSCOPS, respectively. To put these numbers in perspective, when male patients were not stratified stratified /strat·i·fied/ (strat´i-fid) formed or arranged in layers.

strat·i·fied
adj.
Arranged in the form of layers or strata.
 by genotype, absolute risk reduction was 2.8% in CARE and 2.5% in WOSCOPS. Approximately 14% of the subjects in these research studies carry the FCAR risk allele.

Investigation of other polymorphisms in the FCAR region indicated that the FCAR Asn92Asn polymorphism was the most likely reason for the observed association of this region of the genome with risk and response. The FCAR polymorphism is located in a region that encodes the IgA-binding domain of the myeloid IgA Fc receptor, also referred to as CD89. The involvement of the myeloid IgA Fc receptor in monocyte monocyte /mono·cyte/ (mon´o-sit) a mononuclear, phagocytic leukocyte, 13µ to 25µ in diameter, with an ovoid or kidney-shaped nucleus, and azurophilic cytoplasmic granules.  activation is consistent with a functional role for this receptor in the pathogenesis of cardiovascular disease.

"This is an exciting discovery and coupled with others that we've made in cardiovascular diseases, contributes to a better understanding of the etiology of heart disease, and helps identify individuals who are more likely to reduce risk by taking a statin as preventative treatment," said Thomas J. White, Ph.D., Chief Scientific Officer at Celera. "Moreover, along with genetic variation in known drug targets and metabolizing enzymes," genetic markers that predict risk for disease may provide a new source of biomarkers for predicting drug efficacy in multiple diseases."

The lead author of the current study was Olga A. Iakoubova, M.D., Ph.D., Project Leader at Celera, and this research study was conducted with collaborators at Harvard Medical School and Harvard School of Public Health, Boston, MA, University of Glasgow and Royal Infirmary, Glasgow, United Kingdom, and Bristol-Myers Squibb Pharmaceutical Research Institute.

About Applera Corporation and Celera Genomics

Applera Corporation consists of two operating groups. Celera Genomics is primarily a molecular diagnostics business that is using proprietary genomics and proteomics discovery platforms to identify and validate novel diagnostic markers, and is developing diagnostic products based on these markers as well as other known markers. Celera Genomics maintains a strategic alliance with Abbott for the development and commercialization of molecular, or nucleic acid-based, diagnostic products, and it is also developing new diagnostic products outside of this alliance. Through its genomics and proteomics research efforts, Celera Genomics is also discovering and validating therapeutic targets, and it is seeking strategic partnerships to develop therapeutic products based on these discovered targets. The Applied Biosystems Group serves the life science industry and research community by developing and marketing instrument-based systems, consumables, software, and services. Customers use these tools to analyze nucleic acids (DNA DNA: see nucleic acid.
DNA
 or deoxyribonucleic acid

One of two types of nucleic acid (the other is RNA); a complex organic compound found in all living cells and many viruses. It is the chemical substance of genes.
 and RNA RNA: see nucleic acid.
RNA
 in full ribonucleic acid

One of the two main types of nucleic acid (the other being DNA), which functions in cellular protein synthesis in all living cells and replaces DNA as the carrier of genetic
), small molecules, and proteins to make scientific discoveries and develop new pharmaceuticals. Applied Biosystems' products also serve the needs of some markets outside of life science research, which we refer to as "applied markets," such as the fields of: human identity testing (forensic and paternity testing); biosecurity, which refers to products needed in response to the threat of biological terrorism and other malicious, accidental, and natural biological dangers; and quality and safety testing, for example in food and the environment. Applied Biosystems is headquartered in Foster City, CA, and reported sales of over $1.9 billion during fiscal 2006. Information about Applera Corporation, including reports and other information filed by the company with the Securities and Exchange Commission, is available at http://www.applera.com, or by telephoning 800.762.6923. Information about Celera Genomics is available at www.celera.com.

Forward-Looking Statements

Certain statements in this press release are forward-looking. These may be identified by the use of forward-looking words or phrases such as "believe," "plan," and "should," among others. These forward-looking statements are based on Applera Corporation's current expectations. The Private Securities Litigation Reform Act The Private Securities Litigation Reform Act of 1995 (PSLRA) implemented several significant substantive changes affecting certain cases brought under the federal securities laws, including changes related to pleading, discovery, liability, class representation and awards fees and  of 1995 provides a "safe harbor" for such forward-looking statements. In order to comply with the terms of the safe harbor, Applera notes that a variety of factors could cause actual results and experience to differ materially from the anticipated results or other expectations expressed in such forward-looking statements. These factors include but are not limited to: (1) Celera Genomics' unproven ability to discover, develop, or commercialize proprietary diagnostic products; (2) intense competition in the industries in which Celera Genomics operate; (3) potential product liability or other claims against Celera Genomics as a result of the testing or use of its products; (4) uncertainty of the availability to Celera Genomics of intellectual property protection, limitations on its ability to protect trade secrets, the risk to it of infringement claims, and the possibility that it may need to license intellectual property from third parties to avoid or settle such claims; (5) legal, ethical, and social issues which could affect demand for Celera Genomics' products; and (6) other factors that might be described from time to time in Applera's filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Applera does not undertake any duty to update this information, including any forward-looking statements, unless required by law.

Copyright[c] 2006. Applera Corporation. All rights reserved. Celera is a registered trademark and Applera, Applied Biosystems and Celera Genomics are trademarks of Applera Corporation or its subsidiaries in the U.S. and/or certain other countries.
COPYRIGHT 2006 Business Wire
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2006, Gale Group. All rights reserved. Gale Group is a Thomson Corporation Company.

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Publication:Business Wire
Article Type:Clinical report
Date:Sep 28, 2006
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