Celera Diagnostics Identifies Gene Variants Associated with Risk for Progressive Liver Disease.

ALAMEDA, Calif. & CHICAGO -- Link Between Genetic Predisposition and Non-Alcoholic Steatohepatitis (NASH) May Enable Less Invasive Diagnostic Tests for Progressive Liver Disease 

Celera Diagnostics today announced finding a genetic variant associated with a greater than 20-fold increase in risk for Non-Alcoholic Steatohepatitis (NASH), a common progressive liver disease that often leads to fibrosis and cirrhosis. In a scientific session at the Annual Digestive Disease Week conference held in Chicago this week, Hongjin Huang, Ph.D., Manager, Liver Diseases at Celera Diagnostics, described the study in which Celera Diagnostics and its collaborators at the University of California at San Francisco discovered the role of several genetic variations in liver disease. Celera Diagnostics is a joint venture between the Applied Biosystems Group (NYSE:ABI) and Celera Genomics Group (NYSE:CRA) of Applera Corporation.

This study linked the risk for NASH to a variant in the gene DDX5, a gene involved in various aspects of RNA metabolism. Celera Diagnostics previously reported an association of variation in the DDX5 gene with an increased risk of fibrosis in patients infected with the hepatitis C virus at the American Association for the Study of Liver Diseases in November 2004. The current study also found a 17-fold increased risk associated with a variant in the gene coding microsomal triglyceride transfer protein (MTP), a gene central to the export of fats from the liver, and a 5-fold reduction in risk for predisposition to NASH onset with 2 other novel variants. In addition, the work confirmed previous reports of 3 variants in MTP that reduce risk for the development of NASH.

It is estimated that more than 12 million Americans are at risk to develop NASH, and the current typical practice to confirm the development of the disease requires invasive biopsy procedures. Non-alcoholic fatty liver disease encompasses a spectrum of liver injury associated with the accumulation of fat into liver cells, or steatohepatitis, in the absence of significant alcohol consumption. This spectrum extends from simple hepatic steatosis fat accumulation, through NASH, to the end-stage lesion of cirrhosis.

"NASH clearly has a complex genetic component, but the role of genes in disease risk and progression is not well understood," said Nathan M. Bass, M.D., Ph.D., Professor of Medicine and Medical Director of the Liver Transplantation Service at the University of California, San Francisco, and a co-author of the study. "Information from this disease association study may have broad implications for understanding factors involved in progressive liver injury in general. These exciting discoveries open a new window for studying the natural history of liver diseases. The etiology of fibrosis and cirrhosis is not fully understood, and these genetic variants open a whole new way for us to explore these dynamic elements in chronic liver diseases."

"Celera Diagnostics is determining how these gene variants and other genetic markers may identify patients whose liver disease from HCV infection or other causes has a high risk of progressing rapidly to liver fibrosis and potentially cirrhosis," said Kathy Ordonez, president of Celera Diagnostics. "The ability to determine individuals at elevated risk for developing liver disease has substantial utility, and these findings are expected to result in new, less invasive diagnostic tests that may aid decisions around timing and frequency of liver biopsies, as well as how and when to treat patients. We believe that using this information to select and treat rapid disease progressors earlier may help prevent irreversible liver damage and improve patient compliance with therapy. These results may also enable more rapid demonstration of efficacy for new drug therapies for treatment of liver fibrosis due to both HCV infection and NASH."

About Non-alcoholic Steatohepatitis (NASH)

Studies of the natural history of simple steatosis suggest that 10-15% of persons with this lesion progress to NASH and of those, between 16-30% will have a progressive course resulting in fibrosis and cirrhosis and ultimately transplantation(1). There are close similarities in metabolic syndrome associations between NASH and cirrhosis of unknown origin, suggesting that a substantial proportion of patients with this type of cirrhosis may have evolved from NASH. The cause of NASH is not yet defined. The strong association of NASH with obesity, diabetes and insulin resistance implicates an underlying metabolic dysfunction(2).

About Celera Diagnostics and Applera Corporation

Celera Diagnostics is a 50/50 joint venture between two Applera Corporation businesses, the Applied Biosystems Group and the Celera Genomics Group. Headquartered in Alameda, CA, Celera Diagnostics is focused on discovery, development, and commercialization of diagnostic products. The Celera Genomics Group, located in Rockville, MD, and South San Francisco, CA, is engaged principally in the discovery and development of targeted therapeutics for cancer, autoimmune, and inflammatory diseases. Celera Genomics is leveraging its proteomic, bioinformatic, and genomic capabilities to identify and validate drug targets, and to discover and develop small molecule therapeutics. It is also seeking to advance therapeutic antibody and selected small molecule drug programs in collaboration with global technology and market leaders. 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 and RNA), small molecules, and proteins to make scientific discoveries, develop new pharmaceuticals, and conduct standardized testing. Applied Biosystems is headquartered in Foster City, CA, and reported sales of $1.7 billion during fiscal 2004. Information about Applera Corporation, including reports and other information filed by the company with the Securities and Exchange Commission, is available at www.applera.com, or by telephoning 800.762.6923.

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 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 Diagnostics' unproven ability to discover, develop, or commercialize proprietary diagnostic products; (2) the risk that clinical trials of products that Celera Diagnostics does discover and develop will not proceed as anticipated or may not be successful, or that such products will not receive required regulatory clearances or approvals; (3) the uncertainty that Celera Diagnostics' products will be accepted and adopted by the market, including the risk that these products will not be competitive with products offered by other companies, or that users will not be entitled to receive adequate reimbursement for these products from third party payors such as private insurance companies and government insurance plans; (4) reliance on existing and future collaborations, including Celera Diagnostics' strategic alliance with Abbott Laboratories, which may not be successful; (5) legal, ethical, and social issues which could affect demand for Celera Diagnostics' 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) 2005. Applera Corporation. All rights reserved. Applied Biosystems is a registered trademark and Applera, Celera, Celera Diagnostics, Celera Genomics, and Celera Discovery System are trademarks of Applera Corporation or its subsidiaries in the US and/or certain other countries.

(1)Charlton MR, Kasparova P, Weston S, Lindor KD, Maorkendler Y, Wiesner RH et al. The frequency of non-alcoholic steatohepatitis as a cause of advanced liver disease. Liver Transpl 2001.

(2)Poonawala A, Nair SP, Thuluvath PJ. Prevalence of obesity and diabetes in patients with cryptogenic cirrhosis: a case-control study. Hepatology 2000; 32(4 Pt 1):689-692.