A meta-analysis suggests the association of reduced serum level of vitamin D and T-allele of Fok1 (rs2228570) polymorphism in the vitamin D receptor gene with celiac disease

Abstract

PurposeAs an immune-modulator, vitamin D is known to regulate immune response and is implicated in disease pathogenesis. Celiac disease (CD) is a systemic autoimmune disease and susceptibility conferred by vitamin D metabolism is under investigation. Studies on the association of vitamin D metabolism and genetic polymorphisms are expected to explain CD pathogenesis. We performed a systematic review–based meta-analysis to investigate the 25(OH)D serum levels and susceptibility conferred by the genetic variants of VDR in CD.MethodsSystematic review was conducted through a web-based literature search following stringent study inclusion–exclusion criteria. The Newcastle–Ottawa Scale and GRADE tools were used to assess the quality of evidence in studies and the study outcome. Cohen's κ value was estimated to access the reviewer's agreement. RevMan 5.4.1 was used to perform the meta-analyses. Weighted mean difference and Meta p-value was assessed for 25(OH)D serum levels. Meta-odds ratio and Z-test p-value were evaluated to estimate the allelic susceptibility of VDR variants.ResultsA total of 8 out of 12 studies were evaluated for “25(OH)D” serum level, while four studies were found eligible for SNPs (Bsm1, Apa1, Fok1, and Taq1) of VDR. Significantly higher levels [WMD = 5.49, p < 0.00001] of 25(OH)D were observed in healthy controls than in patients with CD. rs2228570-T (Fok1) [Meta-OR = 1.52, p = 0.02] was confirmed to be predisposing allele for CD.ConclusionReduced serum level of 25(OH)D and association of Fok1 T-allele of VDR confirmed in this study plays a critical role in immunomodulation and maintaining barrier integrity, which is majorly implicated in CD.

Relationship between Vitamin D Levels and Pediatric Celiac Disease: A Systematic Review and Meta-analysis

“…These issues may be affected by various factors during childhood. The Fok1 T-allele of vitamin D receptor has association with serum 25(OH)D de ciency in patients with CD, which plays a critical role in immunomodulation and maintaining barrier integrity [57] . The current metaanalysis shows an association between VitD levels and the de ciency and CD, whether it is involved or not in the pathogenesis cannot be ruled out.…”

VDR Gene Single Nucleotide Polymorphisms and Autoimmunity: A Narrative Review

“…CD patients have lower Vitamin D levels but higher levels of 1,25-(OH) 2 D 3 than HC patients [52]. A recent review [53] collected data from four papers that investigated VDR SNPs in CD (176 CD and 402 HC). FokI T allele was associated with a higher CD risk (p = 0.02, OR = 1.52, 95% CI = 1.06-2.18), whereas ApaI, BsmI, and TaqI SNPs were not associated with CD (Table 3).…”

Vitamin D: An Overview of Gene Regulation, Ranging from Metabolism to Genomic Effects

“…The presence of site “F” results in a three-amino-acid-shortened protein, which is characterized by increased transcriptional activity. FokI , in particular, the F-allele, as well as having functional consequences on the structure of the vitamin D receptor, is associated with lower serum 25(OH)D levels [ 28 , 58 ]. TaqI (rs731236) is located in exon 9 of the VDR gene, and consists of T > C substitution.…”

“…Other genes indirectly involved in the control of vitamin D homeostasis and expression have also been studied, despite the evidence being less overt. For example, intracellular domain polymorphisms of the calcium-sensing receptor (CaSR), and polymorphisms of cubilin were studied; however, no associations with vitamin D homeostasis were observed [ 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 ]. Interestingly, a study investigated the impact of FGF23 gene variation on phosphate homeostasis and bone health, detecting nine FGF23 polymorphisms, three of which were quite common: rs3832879, rs7955866, and rs11063112 [ 76 ].…”

“…Interestingly, a study investigated the impact of FGF23 gene variation on phosphate homeostasis and bone health, detecting nine FGF23 polymorphisms, three of which were quite common: rs3832879, rs7955866, and rs11063112 [ 76 ]. A study showed significant correlations between the RXR SNVs rs3132299 or rs9409929 and 1,25(OH)D, as well as between rs877954 and 25(OH)D levels [ 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 ].…”