RT Journal Article
SR Electronic
T1 Angiotensinogen and transforming growth factor β1: novel genes in the pathogenesis of Crohn’s disease
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP e51
OP e51
DO 10.1136/jmg.2005.040477
VO 43
IS 10
A1 G E Hume
A1 E V Fowler
A1 D Lincoln
A1 R Eri
A1 D Templeton
A1 T H Florin
A1 J A Cavanaugh
A1 G L Radford-Smith
YR 2006
UL http://jmg.bmj.com/content/43/10/e51.abstract
AB 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 β1 (TGFβ1) 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 TGFβ1 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 TGFβ1 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.