Polymorphism in the Vitamin D Receptor Gene Decreases the Risk of Perianal Fistulas in Crohn's Disease.

BACKGROUND

Vitamin D, through the activation of its receptor (VDR), plays an immunomodulatory role in the gastrointestinal tract. Single-nucleotide polymorphisms (SNPs) in the VDR gene have been associated with Crohn's disease (CD) risk, and patients carrying the polymorphism in this gene run a higher risk of developing a penetrating behavior.

AIMS

We analyzed the association of , , , and SNPs in the gene with the clinical characteristics of CD.

METHODS

Four polymorphisms identified in the gene (, , , and ) were genotyped in blood samples from CD patients (n = 115) by using PCR-RFLP. The disease's location and behavior and the presence of perianal fistulas were collected from each patient. Intestinal fibroblasts from ileal resections of CD patients (n = 10) were genotyped, and the expression of fibrotic and inflammatory markers was analyzed by RT-PCR.

RESULTS

The data reveal no association between any of the polymorphisms and CD risk. A strong linkage disequilibrium was detected between and both and , which in turn were strongly associated. Homozygosis or heterozygosis for the a allele of the SNP or b allele of the SNP was significantly associated with a lower risk of a penetrating behavior, while the aa genotype was associated with a lower risk of perianal fistulas. Fibroblasts carrying the aa genotype expressed lower levels of fibrotic and inflammatory markers.

CONCLUSION

The aa genotype of the SNP in the gene is associated with a lower risk of perianal fistulas in CD and a reduced expression of fibrotic and inflammatory markers in intestinal fibroblasts.