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Molecular classification of psoriasis disease-associated genes through pharmacogenomic expression profiling

The Pharmacogenomics Journal volume 1, pages 272–287 (2001)Cite this article

Abstract

Psoriasis is recognized as the most common T cell-mediated inflammatory disease in humans. Genetic linkage to as many as six distinct disease loci has been established but the molecular etiology and genetics remain unknown. To begin to identify psoriasis disease-related genes and construct in vivo pathways of the inflammatory process, a genome-wide expression screen of multiple psoriasis patients was undertaken. A comprehensive list of 159 genes that define psoriasis in molecular terms was generated; numerous genes in this set mapped to six different disease-associated loci. To further interpret the functional role of this gene set in the disease process, a longitudinal pharmacogenomic study was initiated to understand how expression levels of these transcripts are altered following patient treatment with therapeutic agents that antagonize calcineurin or NF-κB pathways. Transcript levels for a subset of these 159 genes changed significantly in those patients who responded to therapy and many of the changes preceded clinical improvement. The disease-related gene map provides new insights into the pathogenesis of psoriasis, wound healing and cellular-immune reactions occurring in human skin as well as other T cell-mediated autoimmune diseases. In addition, it provides a set of candidate genes that may serve as novel therapeutic intervention points as well as surrogate and predictive markers of treatment outcome.

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Acknowledgements

The authors would like to thank the many patients and volunteers who donated biopsy samples for these studies. Expert technical assistance was provided by Mary Bozza, Yared Tekabe, John P Kim and Lori Casciotti. We would also like to thank Maryann Whitley, William Mounts, John Ryan and Gene Brown for many thoughtful discussions and assistance in data analysis and experimental design. This work was supported in part by grant GM-42461, from the National Institutes of Health. This work has previously been presented in abstract form at the 61st Annual Meeting of the Society for Investigative Dermatology, Chicago, IL, May 10–14, 2000.

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Authors and Affiliations

  1. Division of Molecular Medicine, Genetics Institute/Wyeth-Ayerst Research, Cambridge, MA, USA

    J L Oestreicher, A J Dorner & W L Trepicchio

  2. Department of Experimental Medicine, Genetics Institute/Wyeth-Ayerst Research, Cambridge, MA, USA

    J Surette & U Schwertschlag

  3. Department of Investigative Dermatology, Rockefeller University, New York, NY, USA

    I B Walters, T Kikuchi, P Gilleaudeau & J G Krueger

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  1. J L Oestreicher
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  2. I B Walters
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  3. T Kikuchi
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  4. P Gilleaudeau
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  5. J Surette
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  6. U Schwertschlag
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  7. A J Dorner
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  8. J G Krueger
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  9. W L Trepicchio
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Correspondence to J G Krueger or W L Trepicchio.

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Oestreicher, J., Walters, I., Kikuchi, T. et al. Molecular classification of psoriasis disease-associated genes through pharmacogenomic expression profiling. Pharmacogenomics J 1, 272–287 (2001). https://doi.org/10.1038/sj.tpj.6500067

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  • DOI: https://doi.org/10.1038/sj.tpj.6500067

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