The Role of Vitamin D Level and Related Single Nucleotide Polymorphisms in Crohn’s Disease

Carvalho, Andre Y. O. M.; Bishop, Karen; Han, Dug Yeo; Ellett, Stephanie; Jesuthasan, Amalini; Lam, Wen Jiun; Ferguson, Lynnette R.

doi:10.3390/nu5103898

Cited by 17 publications

(17 citation statements)

References 45 publications

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“…The role of vitamin D in intestinal homeostasis has been shown through regulation of autophagy (43) and tight junctions (44). Genetic polymorphisms in VDR affect variations in serum vitamin D concentrations (45), and further studies have shown that VDR mediates microbe-host interactions (32). Consistent with a prior report (46), the cation/carnitine transporter SLC22A5 showed universal downregulation across CD TI (FDR 1.42E-12), CD colon (FDR 2.31E-16), and UC colon (FDR 1.37E-27; Figure 8H).…”

Section: Resultsmentioning

confidence: 99%

Characterization of candidate genes in inflammatory bowel disease–associated risk loci

Peloquin¹,

Goel²,

Kong³

et al. 2016

JCI Insight

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GWAS have linked SNPs to risk of inflammatory bowel disease (IBD), but a systematic characterization of disease-associated genes has been lacking. Prior studies utilized microarrays that did not capture many genes encoded within risk loci or defined expression quantitative trait loci (eQTLs) using peripheral blood, which is not the target tissue in IBD. To address these gaps, we sought to characterize the expression of IBD-associated risk genes in disease-relevant tissues and in the setting of active IBD. Terminal ileal (TI) and colonic mucosal tissues were obtained from patients with Crohn’s disease or ulcerative colitis and from healthy controls. We developed a NanoString code set to profile 678 genes within IBD risk loci. A subset of patients and controls were genotyped for IBD-associated risk SNPs. Analyses included differential expression and variance analysis, weighted gene coexpression network analysis, and eQTL analysis. We identified 116 genes that discriminate between healthy TI and colon samples and uncovered patterns in variance of gene expression that highlight heterogeneity of disease. We identified 107 coexpressed gene pairs for which transcriptional regulation is either conserved or reversed in an inflammation-independent or -dependent manner. We demonstrate that on average approximately 60% of disease-associated genes are differentially expressed in inflamed tissue. Last, we identified eQTLs with either genotype-only effects on expression or an interaction effect between genotype and inflammation. Our data reinforce tissue specificity of expression in disease-associated candidate genes, highlight genes and gene pairs that are regulated in disease-relevant tissue and inflammation, and provide a foundation to advance the understanding of IBD pathogenesis.

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Section: Resultsmentioning

confidence: 99%

Characterization of candidate genes in inflammatory bowel disease–associated risk loci

Peloquin¹,

Goel²,

Kong³

et al. 2016

JCI Insight

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“…These authors correlated low concentrations of 25(OH) D with age and low exposure to sunlight. 31 Polymorphism analyzed in our study has been frequently studied with regard to its contribution to the development of osteoporosis in populations all over the world. The results remained equivocal or even contradictory.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D receptor (VDR) TaqI polymorphism, vitamin D and bone mineral density in patients with inflammatory bowel diseases

et al. 2019

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“…One study examined the influence of VDR polymorphisms on serum vitamin D levels [ 40 ] (not included in Table 1 ) showing a significant association of variants of the TaqI and the signal peptide, CUB domain, and EGF-like 3 (SCUBE3, rs732594) genes, the latter encodes for a protein involved in the VDR pathway, in CD patients, whereas ApaI and SCUBE3 and two variants of PHD finger protein-11 (PHF-11) gene, namely, rs2980 and rs2981, showed a significant association with serum vitamin D levels in CD patients. PHF-11 variants have been shown to be involved with vitamin D levels in other pathologies, such as asthma [ 41 ].…”

Section: Vdr Polymorphisms In Ibdmentioning

confidence: 99%

Vitamin D and Inflammatory Bowel Disease

Ardesia

Ferlazzo

Fries

2015

BioMed Research International

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Vitamin D deficiency has been recognized as an environmental risk factor for Crohn's disease since the early 80s. Initially, this finding was correlated with metabolic bone disease. Low serum 25-hydroxyvitamin D levels have been repeatedly reported in inflammatory bowel diseases together with a relationship between vitamin D status and disease activity. Subsequently, low serum vitamin D levels have been reported in various immune-related diseases pointing to an immunoregulatory role. Indeed, vitamin D and its receptor (VDR) are known to interact with different players of the immune homeostasis by controlling cell proliferation, antigen receptor signalling, and intestinal barrier function. Moreover, 1,25-dihydroxyvitamin D is implicated in NOD2-mediated expression of defensin-β2, the latter known to play a crucial role in the pathogenesis of Crohn's disease (IBD1 gene), and several genetic variants of the vitamin D receptor have been identified as Crohn's disease candidate susceptibility genes. From animal models we have learned that deletion of the VDR gene was associated with a more severe disease. There is a growing body of evidence concerning the therapeutic role of vitamin D/synthetic vitamin D receptor agonists in clinical and experimental models of inflammatory bowel disease far beyond the role of calcium homeostasis and bone metabolism.

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The Role of Vitamin D Level and Related Single Nucleotide Polymorphisms in Crohn’s Disease

Cited by 17 publications

References 45 publications

Characterization of candidate genes in inflammatory bowel disease–associated risk loci

Characterization of candidate genes in inflammatory bowel disease–associated risk loci

Vitamin D receptor (VDR) TaqI polymorphism, vitamin D and bone mineral density in patients with inflammatory bowel diseases

Vitamin D and Inflammatory Bowel Disease

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