A microarray screen for novel candidate genes in coeliac disease pathogenesis

Diosdado, B.; Wapenaar, M. C.; Franke, I.; 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.
July 2004
Gut;Jul2004, Vol. 53 Issue 7, p944
Academic Journal
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 Ill lesions of seven patients exposed to gluten with four patients on a gluten free diet. Results: Comparing Marsh Ill 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.


Related Articles

  • Survival in refractory coeliac disease and enteropathy-associated T-cell lymphoma: retrospective evaluation of single-centre experience. Al-toma, A.; Verbeek, W. H. M.; Hadithi, M.; von Blomberg, B. M. E.; Mulder, C. J. J. // Gut;Oct2007, Vol. 56 Issue 10, p1373 

    Background: Coeliac disease may be regarded as refractory disease (RCD) when symptoms persist or recur despite strict adherence to a gluten-free diet. RCD may be subdivided into types I and II with a phenosypically normal and aberrant intraepithelial 1-cell population, respectively. RCD I seems...

  • Altered gene expression in highly purified enterocytes from patients with active coeliac disease. Bracken, Suzanne; Byrne, Greg; Kelly, Jacinta; Jackson, John; Feighery, Conleth // BMC Genomics;2008, Vol. 9, Special section p1 

    Background: Coeliac disease is a multifactorial inflammatory disorder of the intestine caused by ingestion of gluten in genetically susceptible individuals. Genes within the HLA-DQ locus are considered to contribute some 40% of the genetic influence on this disease. However, information on other...

  • Linkage analysis of HLA and candidate genes for celiac disease in a North American family-based study. Neuhausen, Susan L.; Feolo, Michael; Farnham, James; Book, Linda; Zone, John J. // BMC Medical Genetics;2001, Vol. 2, p12 

    Background: Celiac disease has a strong genetic association with HLA. However, this association only explains approximately half of the sibling risk for celiac disease. Therefore, other genes must be involved in susceptibility to celiac disease. We tested for linkage to genes or loci that could...

  • Six new coeliac disease loci replicated in an Italian population confirm association with coeliac disease. Romanos, J.; Barisani, D.; Trynka, G.; Zhernakova, A.; Bardella, M. I.; Wijmenga, C. // Journal of Medical Genetics;Jan2009, Vol. 46 Issue 1, p60 

    Background and aims: The first genome wide association study on coeliac disease (CD) and its follow-up have identified eight new loci that contribute significantly towards CD risk. Seven of these loci contain genes controlling adaptive immune responses, including 1L21/L21 (4q27), RGS1 (1q31),...

  • Proteins Transform DNA into 'Molecular Velcro'.  // Ascribe Newswire: Medicine;6/4/2004, p175 

    Proteins critical for compacting DNA in preparation for cell division actually interact with the double helix to fashion it into a kind of molecular Velcro, researchers have discovered. The successful manipulation of a single DNA molecule with condensin proteins attached makes it plausible to...

  • High rate of mutation reporter gene inactivation during human T cell proliferation. Gabdoulkhakova, Aida; Henriksson, Gunnel; Avkhacheva, Nadezhda; Sofin, Alexander; Bredberg, Anders // Immunogenetics;Feb2007, Vol. 59 Issue 2, p135 

    Caspase activation and degradation of deoxyribonucleic acid (DNA) damage response factors occur during in vitro T-cell proliferation, and an increased frequency of hypoxanthine-guanine phosphoribosyltransferase (HPRT)-negative variants have been reported in conditions associated with in vivo...

  • Opposing functions of PLAG1 in pleomorphic adenoma: a microarray analysis of PLAG1 transgenic mice. Wang, Yang; Shang, Wenjun; Lei, Xia; Shen, Shukun; Zhang, Hongxin; Wang, Zhugang; Huang, Lei; Yu, Zhiwei; Ong, Huishan; Yin, Xuelai; Yang, Wenjun; Zhang, Chenping // Biotechnology Letters;Sep2013, Vol. 35 Issue 9, p1377 

    Over-expression of the proto-oncogene pleomorphic adenoma gene 1 (PLAG1) plays a crucial role in the formation of pleomorphic adenoma, which is the most common type of salivary gland tumor. To understand the molecular mechanisms governing PLAG1-mediated tumorigenesis, we used a microarray-based...

  • Mechanism-Based Screen for G1/S Checkpoint Activators Identifies a Selective Activator of EIF2AK3/PERK Signalling. Stockwell, Simon R.; Platt, Georgina; Barrie, S. Elaine; Zoumpoulidou, Georgia; te Poele, Robert H.; Aherne, G. Wynne; Wilson, Stuart C.; Sheldrake, Peter; McDonald, Edward; Venet, Mathilde; Soudy, Christelle; Elustondo, Frédéric; Rigoreau, Laurent; Blagg, Julian; Workman, Paul; Garrett, Michelle D.; Mittnacht, Sibylle // PLoS ONE;Jan2012, Vol. 7 Issue 1, p1 

    Human cancers often contain genetic alterations that disable G1/S checkpoint control and loss of this checkpoint is thought to critically contribute to cancer generation by permitting inappropriate proliferation and distorting fate-driven cell cycle exit. The identification of cell permeable...

  • It's Not Time to Put Away the Biopsy Forceps. Murray, Joseph A. // American Journal of Gastroenterology;Apr1999, Vol. 94 Issue 4, p869 

    Introduces the article "Sensitivity of Antiendomysium and Antigliadin Antibodies in Untreated Celiac Disease: Disappointing in Clinical Practice," by K. Rostami, J. Kerckhaert, R. Tiemessen, et al.


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics