Skip navigation
Skip navigation

Angiotensinogen and transforming growth factor  1: novel genes in the pathogenesis of Crohn's disease

Hume, G E; Fowler, E V; Lincoln, D; Eri, R; Templeton, D; Florin, T H; Cavanaugh, J A; Radford-Smith, G L

Description

BACKGROUND Angiotensin peptides may act locally as cytokines in several organ systems with elevated mucosal levels present in Crohn's disease. A variant in the angiotensinogen gene promoter results in increased peptide production, while transforming growth factor beta1 (TGFbeta1) codon 25 variants demonstrate variable peptide production, predisposing to fibrosis in several organs. AIMS Conduct an Australian-based analysis of the angiotensinogen-6 variant in two independent inflammatory bowel...[Show more]

dc.contributor.authorHume, G E
dc.contributor.authorFowler, E V
dc.contributor.authorLincoln, D
dc.contributor.authorEri, R
dc.contributor.authorTempleton, D
dc.contributor.authorFlorin, T H
dc.contributor.authorCavanaugh, J A
dc.contributor.authorRadford-Smith, G L
dc.date.accessioned2016-04-07T01:02:14Z
dc.date.available2016-04-07T01:02:14Z
dc.identifier.issn1468-6244
dc.identifier.urihttp://hdl.handle.net/1885/100972
dc.description.abstractBACKGROUND Angiotensin peptides may act locally as cytokines in several organ systems with elevated mucosal levels present in Crohn's disease. A variant in the angiotensinogen gene promoter results in increased peptide production, while transforming growth factor beta1 (TGFbeta1) codon 25 variants demonstrate variable peptide production, predisposing to fibrosis in several organs. AIMS Conduct an Australian-based analysis of the angiotensinogen-6 variant in two independent inflammatory bowel disease (IBD) cohorts, and examine the role of angiotensinogen-6 and TGFbeta1 codon 25 variants in shaping Crohn's disease phenotype. METHODS IBD Patients (Crohn's disease = 347, ulcerative colitis = 147) and CD families (n = 148) from two cohorts, together with 185 healthy controls were genotyped for angiotensinogen-6. Genotype-phenotype analyses were performed for both angiotensinogen-6 and TGFbeta1 codon 25. RESULTS Angiotensinogen-6 AA genotype was significantly associated with Crohn's disease (p = 0.007, OR = 2.38, CI = 1.32-4.32) in cohort 1, but not in the smaller cohort 2 (p = 0.19). The association remained significant when the two cohorts were combined (p = 0.008), and in a TDT family analysis (p = 0.03). TGF 1 codon 25 was associated with stricturing Crohn's disease (p = 0.01, OR = 2.63, CI = 1.16-5.88) and a shorter time to intestinal resection (p = 0.06). CONCLUSIONS The association of the angiotensinogen-6 variant with Crohn's disease supports a potential role for angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists in disease treatment.
dc.format5 pages
dc.publisherBMJ Publishing Group
dc.rights© BMJ Publishing Group
dc.sourceJournal of Medical Genetics
dc.subjectadolescent
dc.subjectadult
dc.subjectangiotensinogen
dc.subjectaustralia
dc.subjectcase-control studies
dc.subjectcohort studies
dc.subjectcolitis, ulcerative
dc.subjectcrohn disease
dc.subjectfemale
dc.subjectgene frequency
dc.subjectgenetic predisposition to disease
dc.subjectgenetic variation
dc.subjectgenotype
dc.subjecthumans
dc.subjectinflammatory bowel diseases
dc.subjectlinkage disequilibrium
dc.subjectmale
dc.subjectphenotype
dc.subjectpolymorphism, genetic
dc.subjectpromoter regions, genetic
dc.subjecttransforming growth factor beta1
dc.titleAngiotensinogen and transforming growth factor  1: novel genes in the pathogenesis of Crohn's disease
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume43
dc.date.issued2006
local.identifier.absfor110311
local.identifier.ariespublicationu4324024xPUB25
local.publisher.urlhttp://www.bmj.com/company/
local.type.statusPublished Version
local.contributor.affiliationHume, G E, Queensland Institute of Medical Research, Australia
local.contributor.affiliationFowler, Elizabeth V, Queensland Institute of Medical Research, Australia
local.contributor.affiliationLincoln, D J, Queensland Institute of Medical Research, Australia
local.contributor.affiliationTempleton, D, Royal Brisbane and Women's Hospital, Australia
local.contributor.affiliationFlorin, T H, Mater Adult Hospital , Australia
local.contributor.affiliationCavanaugh, Juleen, College of Medicine, Biology and Environment, CMBE ANU Medical School, ANU Medical School, The Australian National University
local.contributor.affiliationRadford-Smith, Graham, Royal Brisbane Hospital, Australia
local.identifier.essn1468-6244
local.bibliographicCitation.issue10
local.bibliographicCitation.startpagee51
local.identifier.doi10.1136/jmg.2005.040477
dc.date.updated2016-06-14T09:01:50Z
local.identifier.scopusID2-s2.0-38149075439
CollectionsANU Research Publications

Download

There are no files associated with this item.


Items in Open Research are protected by copyright, with all rights reserved, unless otherwise indicated.

Updated:  19 May 2020/ Responsible Officer:  University Librarian/ Page Contact:  Library Systems & Web Coordinator