Analysis of mucosal gene expression in inflammatory bowel disease by parallel oligonucleotide arrays

DNA arrays capable of simultaneously measuring expression of thousands of g enes in clinical specimens from affected and normal individuals have the po tential to provide information about disease pathogenesis not previously po ssible. Few studies have applied mRNA profiling to diseases involving compl ex tissues like the intestinal mucosa, reflecting the unique challenges inh erent to this type of analysis. We report the analysis of mucosal gene expr ession in ulcerative colitis (UC) patients and inflamed and noninflamed con trol specimens. Genes can be used as markers for cell recruitment, activati on, and mucosal synthesis of immunoregulatory molecules. Self-organizing ma ps were applied to cluster and analyze gene expression patterns and were pa ired with histopathological scores to identify genes associated with increa sed disease activity. Clustering was achieved on the basis of differences i n expression levels across individual specimens. Several inflammatory media tors were identified as likely determinants of characteristic histological features of active UC. These results provide proof of principle for applica tion of functional genomics to larger inflammatory bowel disease population s for gene discovery, to facilitate identification of disease subgroups on the basis of gene expression signatures, and for prediction of disease beha vior or optimal therapeutic intervention.