Article

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

Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Switzerland.
Pharmacogenetics and Genomics (Impact Factor: 3.45). 09/2011; 21(9):559-64. DOI: 10.1097/FPC.0b013e328348f70c
Source: PubMed

ABSTRACT 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.
Using TaqMan SNP technology, we have genotyped 884 individuals (636 IBD cases and 248 non-IBD controls) for the two DBP variants.
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).
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.

1 Follower
 · 
187 Views
  • Source
    Inflammatory Bowel Diseases 01/2012; 18(7):1391-3. DOI:10.1002/ibd.22854 · 5.48 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Inflammatory bowel disease (IBD) has classically been associated with malnutrition and weight loss, although this has become less common with advances in treatment and greater proportions of patients attaining clinical remission. However, micronutrient deficiencies are still relatively common, particularly in CD patients with active small bowel disease and/or multiple resections. This is an updated literature review of the prevalence of major micronutrient deficiencies in IBD patients, focusing on those associated with important extraintestinal complications, including anemia (iron, folate, vitamin B12) bone disease (calcium, vitamin D, and possibly vitamin K), hypercoagulability (folate, vitamins B6, and B12), wound healing (zinc, vitamins A and C), and colorectal cancer risk (folate and possibly vitamin D and calcium). (Inflamm Bowel Dis 2012).
    Inflammatory Bowel Diseases 01/2012; 18(10):1961-81. DOI:10.1002/ibd.22906 · 5.48 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Understanding of the role of vitamin D in health and disease has increased markedly in the past decade, with its involvement extending well beyond traditional roles in calcium and phosphate homeostasis and musculoskeletal health. This conceptual expansion has been underpinned by identification and exploration of components of this axis including vitamin D-binding protein, key enzymes and receptors in multiple cell types, and a greater recognition of nonclassical autocrine and paracrine effects. Its influence in IBD remains uncertain. To review the role of vitamin D in bone health, immune regulation and cancer prevention in IBD, and to outline practical issues and limitations of its use. An extensive online literature review including PubMed and Medline. In patients with IBD, the vitamin D axis provides an important and often underutilised pathway to preserving bone health. Furthermore, an exciting body of clinical and basic science research demonstrates that these pathways may have an integral part to play in regulation of the immune response in IBD, through effects on the intestinal barrier, antigen presenting cells and adaptive T cells. The possibility of chemoprevention requires further study. The optimal target level of 25-hydroxy vitamin D in patients with IBD is currently uncertain, as is the best therapeutic modality. Study of vitamin D pathways may result in the development of relatively inexpensive therapeutic options to optimise patient outcomes. Further prospective clinical research is required to address efficacy and long-term safety.
    Alimentary Pharmacology & Therapeutics 06/2012; 36(4):324-44. DOI:10.1111/j.1365-2036.2012.05181.x · 4.55 Impact Factor