A microarray screen for novel candidate genes in coeliac disease pathogenesis

• Published in: Gut Vol. 53; no. 7; pp. 944 - 951
• Main Authors: Diosdado, B, Wapenaar, M C, Franke, L, Duran, K J, Goerres, M J, Hadithi, M, Crusius, J B A, Meijer, J W R, Duggan, D J, Mulder, C J J, Holstege, F C P, Wijmenga, C
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Society of Gastroenterology 01.07.2004; BMJ; BMJ Publishing Group LTD; Copyright 2004 by Gut
• Subjects: Adult; Aged; Aged, 80 and over; antigen presenting cells; APC; Biological and medical sciences; Biopsy; Celiac disease; Celiac Disease - diet therapy; Celiac Disease - genetics; Celiac Disease - pathology; Cell growth; cell signalling; Child, Preschool; chip; coeliac disease; Disease; Duodenum - pathology; expression profiling; Female; Gastroenterology. Liver. Pancreas. Abdomen; gene expression; Gene Expression Profiling - methods; Gene Expression Regulation; Genes; Genetic engineering; Genetic Predisposition to Disease; Genomics; Gluten; Glutens - administration & dosage; Histology; HLA; human leucocyte antigen; Humans; IFN; interferon; interleukin; Intestinal Mucosa - pathology; Male; Marsh; Medical sciences; microarray; Middle Aged; Oligonucleotide Array Sequence Analysis - methods; Other diseases. Semiology; Pathogenesis; Patients; Reverse Transcriptase Polymerase Chain Reaction; reverse transcription-polymerase chain reaction; RT-PCR; Small Intestine; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Studies; T helper; Immunopathology; Gene; Intestinal malabsorption; Pathogenesis; Gastroenterology; Digestive diseases; Intestinal disease; Coeliac disease
• ISSN: 0017-5749; 1468-3288; 1458-3288
• DOI: 10.1136/gut.2003.018374

Background and aims: The causative molecular pathways underlying the pathogenesis of coeliac disease are poorly understood. To unravel novel aspects of disease pathogenesis, we used microarrays to determine changes in gene expression of duodenal biopsies. Methods: cDNA microarrays representing 19 200 genes were used to compare gene expression profiles of duodenal biopsies from 15 coeliac disease patients with villous atrophy (Marsh III) and seven control individuals with normal biopsies (Marsh 0). In addition, the specific effect of gluten was studied by comparing the expression profiles of Marsh III lesions of seven patients exposed to gluten with four patients on a gluten free diet. Results: Comparing Marsh III with Marsh 0 lesions identified 109 genes that differed significantly (p<0.001) in expression levels between patients and controls. A large number of these genes have functions in proliferation and differentiation pathways and might be important for correct development of crypt-villous units. Alterations in these pathways may lead to the characteristic hyperplasia and villous atrophy seen in coeliac disease. The analyses also revealed 120 differentially expressed genes (p<0.005) when comparing patients on a gluten free diet with those exposed to gluten. These genes further strengthen our observation of increased cell proliferation in the presence of gluten. Conclusions: Our study provides new candidate genes in the pathogenesis of coeliac disease. Based on our results, we hypothesise that villous atrophy in coeliac disease patients is due to failure in cell differentiation. These genes are involved in pathways not previously implicated in coeliac disease pathogenesis and they may provide new targets for therapy.