Extraintestinal manifestations and complications in inflammatory bowel disease: from shared genetics to shared biological pathways.
Inflamm Bowel Dis
; 20(6): 987-94, 2014 Jun.
Article
em En
| MEDLINE
| ID: mdl-24739630
ABSTRACT
BACKGROUND:
The clinical presentation of the inflammatory bowel diseases (IBD) is extremely heterogenous and is characterized by various extraintestinal manifestations and complications (EIM). Increasing genetic insight for IBD and EIM shows multiple shared susceptibility loci. We hypothesize that, next to these overlapping genetic risk loci, distinct disease pathways are shared between IBD and EIM.METHODS:
The overlapping genetic risk loci for IBD and its EIM were searched in literature. We assessed shared disease pathways by performing an extensive pathway analysis by protein-protein interaction and cotranscriptional analysis, using both publicly available and newly developed databases.RESULTS:
Reliable genetic data were available for primary sclerosing cholangitis, ankylosing spondylitis, decreased bone mineral density, colorectal carcinoma, gallstones, kidney stones, and deep venous thrombosis. We found an extensive overlap in genetic risk loci, especially for IBD and primary sclerosing cholangitis and ankylosing spondylitis. We identified 370 protein-protein interactions, of which 108 are statistically specific. We identified 446 statistically specific cotranscribed gene pairs. The interactions are shown to cluster in specific biological pathways.CONCLUSIONS:
We show that the pathogenetic overlap between IBD and its EIM extends beyond shared risk genes to distinctive shared biological pathways. We define genetic background as a risk factor for IBD-EIM alongside known mechanisms such as malabsorption and medication. Clustering patients based on distinctive pathways may enable stratification of patients to predict development of EIM.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Espondilite Anquilosante
/
Colangite Esclerosante
/
Neoplasias Colorretais
/
Doenças Inflamatórias Intestinais
/
Nefrolitíase
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Inflamm Bowel Dis
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Holanda