Celera Identifies Two Genetic Variations Predisposing Individuals to Increased Risk for Psoriasis.Discoveries Present Opportunities for Therapeutic and Pharmacogenomic Product Development Based on Psoriasis Disease Pathways ROCKVILLE, Md. -- Celera (NYSE NYSE See: New York Stock Exchange : CRA See Community Reinvestment Act. ), an Applera Corporation business, today announced the publication of its findings that variants in two genes (IL12B and IL23R) involved in regulating the behavior of cells of the immune system immune system Cells, cell products, organs, and structures of the body involved in the detection and destruction of foreign invaders, such as bacteria, viruses, and cancer cells. Immunity is based on the system's ability to launch a defense against such invaders. independently contribute to psoriasis risk. Individuals who carry two copies of the risk alleles for both these genes, which occur in approximately 25 percent of Caucasians, were found to have a three-fold increased risk for psoriasis relative to individuals with certain other genotypes of these genes. These research findings provide genetic evidence to support the ongoing development of therapeutics that target the interleukin-12 and interleukin-23 (IL-12 and IL-23) pathways. This publication is currently available on the American Journal of Human Genetics' website at http://www.journals.uchicago.edu/AJHG/, and will appear in the February 2007 print edition. "The identification of these two psoriasis susceptibility genes provides additional justification for targeting these pathways with new therapeutics for psoriasis and suggests that IL-23 may be the relevant cytokine Cytokine Any of a group of soluble proteins that are released by a cell to send messages which are delivered to the same cell (autocrine), an adjacent cell (paracrine), or a distant cell (endocrine). ," said Gerald G. Krueger, M.D., Professor of Dermatology and Benning Presidential Endowed Chair at the University of Utah The University of Utah (also The U or the U of U or the UU), located in Salt Lake City, is the flagship public research university in the state of Utah, and one of 10 institutions that make up the Utah System of Higher Education. , Salt Lake City, UT, and co-author on this publication. "Further studies should help determine whether any of the identified risk alleles are also associated with response to therapy and could help determine the most effective dosage of new monoclonal antibody therapies currently in clinical trials." A single nucleotide polymorphism Noun 1. single nucleotide polymorphism - (genetics) genetic variation in a DNA sequence that occurs when a single nucleotide in a genome is altered; SNPs are usually considered to be point mutations that have been evolutionarily successful enough to recur in a in the IL12B gene was identified in a multi-tiered case-control association study of psoriasis in three independent Caucasian North American North American named after North America. North American blastomycosis see North American blastomycosis. North American cattle tick see boophilusannulatus. sample sets (1,446 cases/1,432 controls), using 25,215 gene-centric SNPs, extending the findings from an earlier smaller Japanese study1. A second risk 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. was identified after Celera researchers resequenced the coding regions of IL12B in 96 individuals with psoriasis and then tested 30 additional IL12B-region SNPs. Because IL12B encodes IL-12p40, a subunit of both the IL-12 and IL-23 cytokines Cytokines Chemicals made by the cells that act on other cells to stimulate or inhibit their function. Cytokines that stimulate growth are called "growth factors. , the authors targeted other genes in these two pathways for follow-up studies and identified two SNPs in IL23R, one of the two IL-23 receptor subunits, which are associated with psoriasis independently of the IL12B SNPs. One of these same IL23R SNPs was recently associated with risk for inflammatory bowel disease inflammatory bowel disease n. Abbr. IBD Any of several incurable and debilitating diseases of the gastrointestinal tract characterized by inflammation and obstruction of parts of the intestine. 2 and at least one of the psoriasis-associated IL12B SNPs was not, therefore providing evidence for both shared and distinct underlying mechanisms of these autoimmune diseases Autoimmune diseases A group of diseases, like rheumatoid arthritis and systemic lupus erythematosus, in which immune cells turn on the body, attacking various tissues and organs. Mentioned in: Complement Deficiencies, Premature Menopause . These genetic findings may provide an explanation for the increased incidence of inflammatory bowel disease in subjects with psoriasis. Monoclonal antibodies directed against the IL12B-encoded IL-12p40 subunit are now in clinical trials by other parties for Crohn's disease Crohn's disease: see colitis. , multiple sclerosis and psoriasis. Preliminary data suggest that one of these biologics is highly effective in the treatment of psoriasis3. Celera intends to work with pharmaceutical partners to determine whether the IL12B and IL23R psoriasis risk alleles identified in the current study are also associated with response to anti-IL-12p40 therapy and/or the most effective dosage of this antibody. "These data suggest that these genes play a fundamental role in the development of psoriasis, and add further support to the premise that common genetic variants contribute to general immune dysregulation and susceptibility to autoimmunity," said Thomas J. White, Ph.D., Chief Scientific Officer of Celera, and co-author on the paper. "In addition to the potential molecular diagnostic and pharmacogenomic opportunities that these findings may present for Celera, we're starting to explore how partners can use these experimental SNP SNP Scottish National Party Noun 1. SNP - (genetics) genetic variation in a DNA sequence that occurs when a single nucleotide in a genome is altered; SNPs are usually considered to be point mutations that have been evolutionarily biomarkers in their development of new biological and small molecule therapies for psoriasis and other autoimmune indications." The senior author on this paper was Ann B. Begovich, Ph.D., Director of Inflammation at Celera, and the study was done in collaboration with the Departments of Dermatology and Human Genetics Human genetics A discipline concerned with genetically determined resemblances and differences among human beings. Technological advances in the visualization of human chromosomes have shown that abnormalities of chromosome number or structure are surprisingly at the University of Utah, Salt Lake City, Genomics Collaborative Division of SeraCare Life Sciences, Cambridge, MA, and LineaGen Research Corporation, Salt Lake City, UT. About Psoriasis Psoriasis is a chronic inflammatory skin disease characterized by thickened thick·en tr. & intr.v. thick·ened, thick·en·ing, thick·ens 1. To make or become thick or thicker: Thicken the sauce with cornstarch. The crowd thickened near the doorway. 2. , scaly scal·y adj. 1. Covered or partially covered with scales. 2. Shedding scales or flakes; flaking. scaly skin condition characterized by scales; scalelike. skin patches that affects between 5.8 and 7.5 million people in the United States. The disease frequently develops in early adulthood and appears about equally in males and females. It is caused by abnormal keratinocyte keratinocyte /ke·rat·i·no·cyte/ (ker-at´in-o-sit) the epidermal cell that synthesizes keratin, known in its successive stages in the layers of the skin as basal cell, prickle cell, and granular cell. proliferation and infiltration of inflammatory cells into the skin. Once psoriasis appears, it is usually a life-long disease; spontaneous improvement is rare and severe disease is usually associated with a progressive increase in the amount of skin surface covered. In the past, doctors have generally treated psoriasis based on the severity of the disease, size of the areas involved, type of psoriasis, and the patient's response to initial treatments using therapies with limiting toxicities4 . Newer treatments have been more selective and less toxic. The genetics of psoriasis are complex and the disease is highly heritable her·i·ta·ble adj. 1. Capable of being passed from one generation to the next; hereditary. 2. Capable of inheriting or taking by inheritance. as evidenced by an increased rate of concordance concordance /con·cor·dance/ (-kord´ins) in genetics, the occurrence of a given trait in both members of a twin pair.concor´dant con·cor·dance n. in monozygotic twins over dizygotic twins (35%-72% vs. 12-23%) and a substantially increased incidence in family members of affected individuals (first-degree relatives 6%). However, it is clear that environmental effects are also responsible for disease susceptibility. About Applera Corporation and Celera Applera Corporation consists of two operating groups. Celera 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 maintains a strategic alliance with Abbott for the development and commercialization of molecular, or nucleic acid-based, diagnostic products, and is also developing new diagnostic products outside of this alliance. Through its genomics and proteomics research efforts, Celera is also discovering and validating therapeutic targets, and has established and 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 is available at http://www.celera.com. 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's unproven ability to discover, develop, or commercialize proprietary diagnostic products; (2) the risk that clinical trials of products that Celera 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's products will be accepted and adopted by the market, including the risk that 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) legal, ethical, and social issues which could affect demand for Celera's' products; and (5) 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 are trademarks of Applera Corporation or its subsidiaries in the U.S. and/or certain other countries. 1 Tsunemi Y et al, (2002) Interlukin-12 p40 gene (IL12B) 3'-untranslated region polymorphism is associated with susceptibility to atopic dermatitis and psoriasis vulgaris. J Dermatol Sci 30:161-166. 2 Duerr, RH et al., (2006) A genome-wide association study A genome-wide association study (GWAS) is an examination of genetic variation across the human genome, designed to identify genetic associations with observable traits, such as blood pressure or weight, or why some people get a disease or condition. identifies IL23R as an inflammatory bowel disease gene. Science 314:1461-1463. 3 Kauffman CL et al., (2004) A phase I study evaluating the safety, pharmacokinetics, and clinical response of a human IL-12 p40 antibody in subjects with plaque psoriasis. J Invest Dermatol. 123:1037 -1044 4 National Institute of Arthritis and Musculoskeletal and Skin Diseases The National Institute of Arthritis and Musculoskeletal and Skin Diseases, or NIAMS, is an institute of the National Institutes of Health, an agency of the United States Department of Health and Human Services. : http://www.niams.nih.gov/hi/topics/psoriasis/psoriasis.htm |
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