Contribution of TNFSF15 gene variants to Crohn's disease susceptibility confirmed in UK population
Article first published online: 13 MAR 2008
Copyright © 2008 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 14, Issue 6, pages 733–737, June 2008
How to Cite
Tremelling, M., Berzuini, C., Massey, D., Bredin, F., Price, C., Dawson, C., Bingham, S. A. and Parkes, M. (2008), Contribution of TNFSF15 gene variants to Crohn's disease susceptibility confirmed in UK population. Inflamm Bowel Dis, 14: 733–737. doi: 10.1002/ibd.20399
- Issue published online: 5 MAY 2008
- Article first published online: 13 MAR 2008
- Manuscript Accepted: 2 JAN 2008
- Manuscript Received: 27 DEC 2007
- Clinical Research Training Fellowship from the Wellcome Trust
- National Association for Colitis and Crohn's Disease
- Crohn's disease;
Background: Identification of Crohn's disease (CD)-associated genetic variants is key to understanding pathogenic pathways underlying disease susceptibility. Recent reports of an association between TNFSF15 variants and CD have been modestly replicated in European populations, suggesting heterogeneity at this locus with stronger CD association in Japanese than European populations.
Methods: We investigated the association between variants in TNFSF15 and CD in 756 CD patients and 636 controls. Disease subphenotype associations were also investigated.
Results:TNFSF15 single nucleotide polymorphism (SNP) variants were associated with CD in our panel with peak odds ratio (OR) 1.2 (95% confidence interval [CI] 1.01–1.41) P = 0.033. The presence of a risk haplotype was replicated for the first time in a European population (frequency 67% in cases and 61% in controls) OR = 1.44 (95% CI 1.23–1.68) P = 0.00012. This result mirrors the UK panel in the index study (Yamazaki et al  Hum Mol Genet 14:3499–3506) but is less significant than that reported in Japanese populations. There was no evidence of association with any individual CD subphenotype.
Conclusions: Variants in TNFSF15 contribute to overall CD susceptibility in European populations, although to a lesser extent than that seen in the Japanese. Further studies to define the precise disease-causing variants as well as targeted functional studies are now required in human CD as TNFSF15 is a potential target for biological therapies.
(Inflamm Bowel Dis 2008)