Novel Genetic Risk Markers for Ulcerative Colitis in the IL2/IL21 Region Are in Epistasis With IL23R and Suggest a Common Genetic Background for Ulcerative Colitis and Celiac Disease

Glas, J.; Stallhofer, Johannes; Ripke, Stephan; Wetzke, Martin; Pfennig, Simone; Klein, Wolfram; Epplen, Jörg T.; Griga, Thomas; Schiemann, U.; Lacher, Martin; Koletzko, Sibylle; Folwaczny, Matthias; Lohse, Peter; Göke, Burkhard; Ochsenkühn, Thomas; Müller‐Myhsok, Bertram; Brand, Stephan

doi:10.1038/ajg.2009.163

Cited by 79 publications

(77 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Upregulation of IL-15 expression by epithelial cells and dendritic cells in the lamina propria seems to also contribute to the altered signaling properties of the CD8+ T cell population (16). In addition, recent genome-wide association studies have provided convincing evidence that the IL-21 gene also is associated with CD (19,20). IL-21 has been shown to stimulate epithelial cells to secrete chemokines, to facilitate the recruitment of immune cells within the inflamed tissue and to modulate the proliferation and function of CD8 + T and NK cells (21).…”

Section: Ppar Signaling Pathway and Cancer-related Proteins Are Involmentioning

confidence: 88%

PPAR Signaling Pathway and Cancer-Related Proteins Are Involved in Celiac Disease-Associated Tissue Damage

Simula

Cannizzaro

Canzonieri

et al. 2010

Mol Med

View full text Add to dashboard Cite

Celiac disease (CD) is an immune-mediated disorder triggered by the ingestion of wheat gliadin and related proteins in genetically predisposed individuals. To find a proteomic CD diagnostic signature and to gain a better understanding of pathogenetic mechanisms associated with CD, we analyzed the intestinal mucosa proteome alterations using two dimensional difference gel electrophoresis (2D-DIGE) coupled with matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF ms) of CD patients with varying degrees of histological abnormalities defined by Marsh criteria and controls. Our results clearly evidenced the presence of two groups of patients: Group A, including controls and Marsh 0-I CD patients; and Group B, consisting of CD subjects with grade II-III Oberhuber-Marsh classification. Differentially expressed proteins were involved mainly in lipid, protein and sugar metabolism. Interestingly, in Group B, several downregulated proteins (FABP1, FABP2, APOC3, HMGCS2, ACADM and PEPCK) were implicated directly in the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Moreover, Group B patients presented a deregulation of some proteins involved in apoptosis/survival pathways: phosphatidylethanolamine-binding protein 1 (PEBP1), Ras-related nuclear protein (Ran) and peroxiredoxin 4 (PRDX4). PEBP1 downregulation and RAN and PRDX4 upregulation were associated with more severe tissue damage. Likewise, IgMs were found strongly upregulated in Group B. In conclusion, our results indicate that a downregulation of proteins involved in PPAR signaling and the modulation of several cancer-related proteins are associated with the highest CD histological score according to Oberhuber-Marsh classification.

show abstract

Section: Ppar Signaling Pathway and Cancer-related Proteins Are Involmentioning

confidence: 88%

PPAR Signaling Pathway and Cancer-Related Proteins Are Involved in Celiac Disease-Associated Tissue Damage

Simula

Cannizzaro

Canzonieri

et al. 2010

Mol Med

View full text Add to dashboard Cite

show abstract

“…Evidence concerning the involvement of a specific variant in this region was not possible due to strong LD in the region. Interestingly, this region has also been shown to associate with type Ⅰ diabetes, rheumatoid arthritis and recently UC, hinting at the presence of a common factor for immune-mediated diseases [115][116][117] . To increase the likelihood of disease-gene identification in this GWAS data, additional non-HLA SNPs were subsequently subjected to genotyping in an even larger replication panel [113,114] .…”

Section: Celiac Diseasementioning

confidence: 99%

Genome-wide association studies - A summary for theclinical gastroenterologist

Melum¹,

Franke²,

Karlsen³

2009

WJG

View full text Add to dashboard Cite

Genome-wide association studies (GWAS) have been applied to various gastrointestinal and liver diseases in recent years. A large number of susceptibility genes and key biological pathways in disease development have been identified. So far, studies in inflammatory bowel diseases, and in particular Crohn's disease, have been especially successful in defining new susceptibility loci using the GWAS design. The identification of associations related to autophagy as well as several genes involved in immunological response will be important to future research on Crohn's disease. In this review, key methodological aspects of GWAS, the importance of proper cohort collection, genotyping issues and statistical methods are summarized. Ways of addressing the shortcomings of the GWAS design, when it comes to rare variants, are also discussed. For each of the relevant conditions, findings from the various GWAS are summarized with a focus on the affected biological systems.

show abstract

“…Accordingly the signature cytokines of Th17 cells (IL-17A, IL-17F, IL-22) are produced in the intestine of CD and UC patients [116,[118][119][120]. Additionally, genome wide association studies have linked polymorphism in Th17-related genes, such as IL-23R and STAT3 with IBD [121][122][123][124]. In line with these associations murine studies have also shown that Th17 cells are involved in numerous autoimmune and chronic inflammatory diseases [2], and IBD is one of these diseases [125]: ROR t deficient mice, which lack Th17 cells, exhibit attenuated experimentally induced autoimmune disease [4].…”

Section: Breakdown Of the Immune Homeostasis In The Intestinementioning

confidence: 99%

Balancing pro- and anti-inflammatory CD4+ T helper cells in the intestine

Gagliani¹,

Huber²

2012

Autoimmune Diseases - Contributing Factors, Specific Cases of Autoimmune Diseases, and Stem Cell and Other Therapies

View full text Add to dashboard Cite

Novel Genetic Risk Markers for Ulcerative Colitis in the IL2/IL21 Region Are in Epistasis With IL23R and Suggest a Common Genetic Background for Ulcerative Colitis and Celiac Disease

Abstract: Similar to other autoimmune diseases such as celiac disease, rheumatoid arthritis, type 1 diabetes, Graves' disease, and psoriatic arthritis, genetic variation in the chromosome 4q27 region predisposes to UC, suggesting a common genetic background for these diseases.

Cited by 79 publications

References 50 publications

PPAR Signaling Pathway and Cancer-Related Proteins Are Involved in Celiac Disease-Associated Tissue Damage

PPAR Signaling Pathway and Cancer-Related Proteins Are Involved in Celiac Disease-Associated Tissue Damage

Genome-wide association studies - A summary for theclinical gastroenterologist

Balancing pro- and anti-inflammatory CD4+ T helper cells in the intestine

Contact Info

Product

Resources

About