Vitamin D receptor gene polymorphism: association with Crohn's disease susceptibility

Background-The vitamin D receptor (VDR) gene represents a strong positional candidate susceptibility gene for inflammatory bowel disease (IBD). The VDR gene maps to a region on chromosome 12 that has been shown to be linked to IBD by genome screening techniques. it is the cellular receptor for 1,25(OH)(2) vitamin D-3 (calcitriol) which has a wide range of different regulatory effects on the immune system. IBD is characterised by activation of the mucosal immune system. Aim-To determine if polymorphisms in the VDR gene are associated with susceptibility to IBD Subjects-European Caucasoids: 158 patients with ulcerative colitis, 245 with Crohn's disease, and 164 cadaveric renal allograft donor controls. Method-Single nucleotide polymorphisms (TaqI, ApaI, and FokI) in VDR were typed in patients with Crohn's disease, ulcerative colitis, and controls by polymerase chain reaction with sequence specific primers. Results-There were significantly more homozygotes for the TaqI polymorphism at codon 352 of exon 8 (genotype tt) among patients with Crohn's disease (frequency 0.22) than patients with ulcerative colitis (0.12) or controls (0.12) (odds ratio 1.99; 95% confidence interval 1.14-3.47; p=0.017). Conclusion-This study provides preliminary evidence for a genetic association between Crohn's disease susceptibility and a gene that lies within one of the candidate regions determined by linkage analysis.