Contribution of TNFSF15 gene variants to Crohn's disease susceptibility confirmed in UK population.
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 [2005] 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.
Tremelling
Mark
M
East Anglia IBD Research Group, Cambridge University Department of Medicine, Addenbrookes Hospital, Cambridge, UK.
Berzuini
Carlo
C
Massey
Dunecan
D
Bredin
Francesca
F
Price
Catherine
C
Dawson
Claire
C
Bingham
Sheila A
SA
Parkes
Miles
M
D000328:Adult; D003424:Crohn Disease / Q000235:genetics*; D004198:Disease Susceptibility; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007564:Japan; D008297:Male; D020641:Polymorphism, Single Nucleotide; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000235:genetics*; D006113:United Kingdom
C117026:TNFSF15 protein, human; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15