Vitamin D Receptor Gene Single Nucleotide Polymorphisms and Association With Vitamin D Levels and Endoscopic Disease Activity in Inflammatory Bowel Disease Patients: A Pilot Study

Abstract

Background: Inflammatory bowel diseases (IBDs) comprise a heterogenous group of chronic gastrointestinal disorders that are multifactorial in etiology. Experimental in vitro and in vivo studies suggest that intestinal vitamin D receptor (VDR) signaling plays a role in modulating the immune response in IBD as a cause and/or a consequence of chronic inflammation.

Aim: The aim of this study is to study the associations between vitamin D receptor gene single nucleotide polymorphisms(SNPs), vitamin D levels, and endoscopic disease activity in IBD.

Methods: This is a cross-sectional analysis of IBD patients who underwent endoscopic evaluation at a tertiary care hospital. Demographic variables, IBD disease type and location, medical therapies, vitamin D levels, and endoscopic disease activity were collected. Colonic biopsies obtained were investigated for the presence of VDR SNPs: ApaI, TaqI, BsmI, FokI, and Tru9I.

Results: Patients in endoscopic remission had higher vitamin D levels compared with those with inflammation found on endoscopy (P = <0.001). Patients with lower vitamin D levels were homozygous for Fok ancestral alleles (P = 0.0045). With regard to endoscopic disease activity, we found no differences in mutations of any of the VDR SNPs in our sample.

Conclusions: The association between the presence of the ancestral FokI and lower vitamin D levels suggests a multifactorial etiology for vitamin D deficiency in IBD. Higher vitamin D levels in those in endoscopic remission compared with lower levels in those with active inflammation suggests that the impact of VDR gene SNP on disease activity may be overcome with replacement therapy.

Keywords: inflammatory bowel disease; vitamin D; vitamin D receptor.

FIGURE 1.

Agarose gel electrophoresis patterns of the 5 SNPs in VDR. A, PCR products digestion with FOKI demonstrate three genotypes (AA, AC, and CC). B, PCR products digestion with APAI (top) demonstrate 3 genotypes (CC, AC, and AA) and TAQI (bottom) demonstrate 3 genotypes (AA, AG, and GG). C, PCR products digestion with BSMI demonstrate 3 genotypes (CC, CT, and TT). D, PCR products digestion with MSEI demonstrate 2 of 3 genotypes (CC, CT, and TT).