title: Association of a common vitamin D-binding protein polymorphism with inflammatory bowel disease.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Switzerland.
authors.forename: Jyrki J
authors.initials: JJ
authors.lastname: Eloranta
authors.forename: Christa
authors.initials: C
authors.lastname: Wenger
authors.forename: Jessica
authors.initials: J
authors.lastname: Mwinyi
authors.forename: Christian
authors.initials: C
authors.lastname: Hiller
authors.forename: Christoph
authors.initials: C
authors.lastname: Gubler
authors.forename: Stephan R
authors.initials: SR
authors.lastname: Vavricka
authors.forename: Michael
authors.initials: M
authors.lastname: Fried
authors.forename: Gerd A
authors.initials: GA
authors.lastname: Kullak-Ublick
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D014809:Vitamin D-Binding Protein / Q000235:genetics*
chemical_list: D014809:Vitamin D-Binding Protein