Genetic variation in DLG5 is associated with inflammatory bowel disease View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2004-05

AUTHORS

Monika Stoll, Brit Corneliussen, Christine M Costello, Georg H Waetzig, Bjorn Mellgard, W Andreas Koch, Philip Rosenstiel, Mario Albrecht, Peter J P Croucher, Dirk Seegert, Susanna Nikolaus, Jochen Hampe, Thomas Lengauer, Stefan Pierrou, Ulrich R Foelsch, Christopher G Mathew, Maria Lagerstrom-Fermer, Stefan Schreiber

ABSTRACT

Crohn disease and ulcerative colitis are two subphenotypes of inflammatory bowel disease (IBD), a complex disorder resulting from gene-environment interaction. We refined our previously defined linkage region for IBD on chromosome 10q23 and used positional cloning to identify genetic variants in DLG5 associated with IBD. DLG5 encodes a scaffolding protein involved in the maintenance of epithelial integrity. We identified two distinct haplotypes with a replicable distortion in transmission (P = 0.000023 and P = 0.004 for association with IBD, P = 0.00012 and P = 0.04 for association with Crohn disease). One of the risk-associated DLG5 haplotypes is distinguished from the common haplotype by a nonsynonymous single-nucleotide polymorphism 113G-->A, resulting in the amino acid substitution R30Q in the DUF622 domain of DLG5. This mutation probably impedes scaffolding of DLG5. We stratified the study sample according to the presence of risk-associated CARD15 variants to study potential gene-gene interaction. We found a significant difference in association of the 113A DLG5 variant with Crohn disease in affected individuals carrying the risk-associated CARD15 alleles versus those carrying non-risk-associated CARD15 alleles. This is suggestive of a complex pattern of gene-gene interaction between DLG5 and CARD15, reflecting the complex nature of polygenic diseases. Further functional studies will evaluate the biological significance of DLG5 variants. More... »

PAGES

476-480

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ng1345

DOI

http://dx.doi.org/10.1038/ng1345

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1039933647

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/15107852


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