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Expression profiling reveals genes involved in psoriasis
Edward R. Winstead


Scientists have identified 159 genes that are expressed differently in persons with psoriasis compared to persons with healthy skin and other types of lesions. By testing the effects of various drugs on the expression of these genes in biopsy tissue, the researchers identified a subset of genes whose expression changed significantly in response to treatment. These are candidates for further study. Psoriatic lesions typically involve an immune response, and the drugs in the study target some aspects of inflammation.

Schematic of comparison of differentially expressed genes. View larger

To identify disease-related gene candidates, William L. Trepicchio, of Wyeth Research in Andover, Massachusetts, and colleagues profiled the expression of 7,000 human genes in affected individuals and controls. Of the 159 genes, several had previously been linked to psoriasis through other methods. Twelve genes were found to be near chromosomal regions likely to contain risk factors for the disease. A certain number of genes has been associated with psoriasis or inflammatory conditions for the first time.

The study was done in collaboration with James G. Krueger, who heads the Laboratory for Investigative Dermatology at The Rockefeller University in New York, and appears in The Pharmacogenomics Journal. The researchers note that changes in gene expression may be a cause of disease or a consequence of the disease process. It is necessary to differentiate between these two possibilities when analyzing the results of genome-wide expression profiles.

To address this question of cause or effect, the researchers analyzed biopsy tissue from patients following drug treatment. They identified a subset of 41 differentially regulated genes that returned to normal levels after medications and prior to the appearance of clinical changes associated with the disease. These genes, the researchers conclude, may cause the development of psoriasis. The drugs were rhIL-11 and Cyclosporin A, which can disrupt the inflammatory process.

"These studies present for the first time a genome-wide expression response to pharmacological intervention in a longitudinal study and indicate that this method has utility in prioritizing disease-associated genes for further functional genomic analysis," the researchers write.

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Oestreicher, J.L. et al. Molecular classification of psoriasis disease-associated genes through pharmacogenomic expression profiling. Pharmacogenomics J 1, 272-287 (2001).

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