Candidate genes colocalized to linkage regions in inflammatory bowel disease

Background and Aims: The genes encoding for tumor necrosis
factor-alpha (TNF-alpha), epidermal growth factor receptor (EGFR)
and the vitamin D receptor (VDR) are colocalized to inflammatory
bowel disease-associated linkage regions on chromosomes 6, 7 and
12. An association study of these gene polymorphisms with
ulcerative colitis or Crohn's disease and a stratification
according to disease phenotypes was performed in order to identify
gentically homogenous subgroups. Patients and Methods: 119 healthy,
unrelated controls, 95 patients with Crohn's disease and 93
patients with ulcerative colitis were genotyped for the (G to A)
-308 TNF-alpha promoter polymorphism on chromosome 6, the codon 497
EGFR polymorphism on chromosome 7 and the Taql polymorphism of the
VDR gene on chromosome 12. After genotyping, patients were
stratified according to the respective disease phenotype. Results:
A disequilibrium in the distribution of the VDR genotypes was found
in patients with ulcerative colitis compared to controls (p =
0.024). In fistulizing and fibrostenotic Crohn's disease the `TT'
genotype was significantly reduced compared with other phenotypes
(p = 0.006), whereas the `tt' genotype was found more frequently (p
= 0.04). The frequency of the WT allele of the EGFR gene was
significantly higher in ulcerative colitis (p = 0.04) than in
controls. Further significant differences, concerning the
associations of the different polymorphisms and disease
susceptibility or clinical phenotypes, were not observed.
Conclusions: Regardless of the disease phenotype, the associations
between the polymorphisms and inflammatory bowel disease
investigated herein are modest, even after stratification for the
disease phenotypes. Hence, these polymorphisms are unlikely to
confer the reported linkage between inflammatory bowel disease and
chromosomes 6, 7 and 12. Copyright (C) 2002 S. Karger AG, Basel.