Insights into psoriasis and other inflammatory diseases from large-scale gene expression studies

Approximately 2% of the Caucasian population is affected by psoriasis (PS); a chronic inflammatory skin disease triggered by both genetic and environm ental risk factors. In addition to a major contribution from the HLA class I region, PS susceptibility loci have been mapped to a number of regions in cluding 1q21, 3q21, 4qter, 14q31-q32, 17q24-q25, 19p13.3 and 20p. Some of t hese overlap with loci implicated in other autoimmune/inflammatory diseases . Global gene expression studies are beginning to provide insights into the etiology of these and other complex diseases. We used Affymetrix oligonucl eotide arrays comprising approximately 12 000 known genes to initiate a mor e comprehensive analysis of the transcriptional changes that occur in invol ved and uninvolved skin of 15 psoriatic patients versus six normal controls . Expression levels of the transcripts detected on the arrays were first us ed to determine the relationship of samples to each other using hierarchica l clustering. This analysis clearly differentiated involved psoriatic skin from uninvolved and normal skin. Clusters of differentially expressed genes with similar expression patterns in the same samples were then identified. Six out of 32 clusters contained a total of 177 transcripts that were diff erentially expressed in involved psoriatic skin versus normal skin. These d ifferences were independent of the gender, age, skin site and HLA class I s tatus of the patient. Ten of the 177 genes were also differentially express ed in uninvolved skin, and several mapped to regions previously shown to ha rbor psoriasis susceptibility loci.