Genetic variants in DLG5 encode a scaffolding protein on chromosome 10q23.
Tumor necrosis factor-alpha, encodes a proinflammatory cytokine on chromosome 6p.
These have recently been reported to be associated with inflammatory bowel disease (IBD).
Dr Mark Tremelling and colleagues studied these variants to seek evidence of association with IBD in a large independent dataset in the England.
The researchers genotyped 1104 unrelated white IBD subjects.
Of these 496 had Crohn's disease, 512 had ulcerative colitis.
| Tumor necrosis factor-857 is associated with ulcerative colitis, and Crohn's|
|Inflammatory Bowel Diseases|
The team reported that 96 had indeterminate colitis from the Cambridge/Eastern panel in the United Kingdom.
The research team also included 760 healthy control subjects.
The team assessed DLG5_113G/A, DLG5_4136C/A, tumor necrosis factor-857C/T, and tumor necrosis factor-1031T/C polymorphisms.
Known Crohn's disease-predisposing variants in CARD15/NOD2 were also genotyped to permit analysis for reported epistatic interactions.
Tumor necrosis factor-857 was shown to be associated with IBD overall.
A formal interaction test showed that tumor necrosis factor-857 is associated equally with ulcerative colitis and Crohn's disease.
The research team found that neither of the DLG5 alleles, however, was associated with IBD.
Subgroup analysis also failed to show evidence of association between either DLG5 allele or genotype frequencies and ulcerative colitis or Crohn's disease.
Stratification of tumor necrosis factor-alpha and DLG5 cases by CARD15 genotype made no significant difference in the strength of associations.
Dr Tremelling's team commented, “We have confirmed an association between the tumor necrosis factor-857 promoter polymorphism and IBD in a large independent United Kingdom dataset but were unable to replicate an association at the previously reported loci within DLG5.”
“This may reflect heterogeneity between the populations, a smaller effect size than originally predicted, or possibly a false-positive result in the original study.”
“Further fine mapping studies of the tumor necrosis factor promoter region and studies assessing functional consequences of tumor necrosis factor promoter polymorphisms are now required in IBD.”