Molecular classification of psoriasis diseaseassociated genes through pharmacogenomic expression profiling

被引：0

作者：

Oestreicher J.L. ^{[1
]}

Walters I.B. ^{[3
]}

Kikuchi T. ^{[3
]}

Gilleaudeau P. ^{[3
]}

Surette J. ^{[2
]}

Schwertschlag U. ^{[2
]}

Dorner A.J. ^{[1
]}

Krueger J.G. ^{[3
]}

Trepicchio W.L. ^{[1
]}

机构：

[1] Division of Molecular Medicine, Genetics Institute, Wyeth-Ayerst Research, Cambridge, MA

[2] Department of Experimental Medicine, Genetics Institute/Wyeth-Ayerst Research, Cambridge, MA

[3] Department of Investigative Dermatology, Rockefeller University, New York, NY

来源：

The Pharmacogenomics Journal | 2001年 / 1卷 / 4期

基金：

美国国家卫生研究院;

关键词：

Cyclosporin a; Gene expression profiling; Inflammation; Microarrays; Psoriasis; Recombinant human interleukin 11 (rhll-11);

D O I：

10.1038/sj.tpj.6500067

中图分类号：

学科分类号：

摘要：

Psoriasis is recognized as the most common T cell-mediated inflammatory disease irthumans. 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. © 2001 Nature Publishing Group All rights reserved.

引用

页码：272 / 287

页数：15

共 5 条

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