Association of a common vitamin D-binding protein polymorphism with inflammatory bowel disease

作者：Eloranta Jyrki J; Wenger Christa; Mwinyi Jessica; Hiller Christian; Gubler Christoph; Vavricka Stephan R; Fried Michael; Kullak Ublick Gerd A^*

来源：Pharmacogenetics and Genomics, 2011, 21(9): 559-564.

DOI：10.1097/FPC.0b013e328348f70c

• Crohn's disease
• inflammatory bowel disease
• ulcerative colitis
• vitamin D homeostasis
• vitamin D-binding protein

Objective Inflammatory bowel diseases (IBDs), Crohn's disease, and ulcerative colitis (UC), are multifactorial disorders, characterized by chronic inflammation of the intestine. A number of genetic components have been proposed to contribute to IBD pathogenesis. In this case-control study, we investigated the association between two common vitamin D-binding protein (DBP) genetic variants and IBD susceptibility. These two single nucleotide polymorphisms (SNPs) in exon 11 of the DBP gene, at codons 416 (GAT > GAG; Asp > Glu) and 420 (ACG > AAG; Thr > Lys), have been previously suggested to play roles in the etiology of other autoimmune diseases.
Methods Using TaqMan SNP technology, we have genotyped 884 individuals (636 IBD cases and 248 non-IBD controls) for the two DBP variants.
Results On statistical analysis, we observed that the DBP 420 variant Lys is less frequent in IBD cases than in non-IBD controls (allele frequencies, P = 0.034; homozygous carrier genotype frequencies, P = 0.006). This inverse association between the DBP 420 Lys and the disease remained significant, when non-IBD participants were compared with UC (homozygous carrier genotype frequencies, P = 0.022) or Crohn's disease (homozygous carrier genotype frequencies, P = 0.016) patients separately. Although the DBP position 416 alone was not found to be significantly associated with IBD, the haplotype DBP_2, consisting of 416 Asp and 420 Lys, was more frequent in the non-IBD population, particularly notably when compared with the UC group ( Odds ratio, 4.390).
Conclusion Our study adds DBP to the list of potential genes that contribute to the complex genetic etiology of IBD, and further emphasizes the association between vitamin D homeostasis and intestinal inflammation.

• 出版日期2011-9