Dataset Information

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:

Purpose

As 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.

Methods

Systematic 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.

Results

A 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.

Conclusion

Reduced 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.

SUBMITTER: Shree T

PROVIDER: S-EPMC9893277 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

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.

Shree Tanya T Banerjee Pratibha P Senapati Sabyasachi S

Frontiers in nutrition 20230119

<h4>Purpose</h4>As 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 ...[more]

PMID: 36741989

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Project description:BackgroundThe goal of this study was to determine if vitamin D receptor (VDR) gene polymorphisms underlie susceptibility to dyslipidemia in a Chinese Han population.MethodsThree tag single nucleotide polymorphisms (SNPs) (rs11574129, rs2228570, and rs739837) were genotyped using TaqMan assays to determine VDR SNP associations with dyslipidemia. We genotyped 877 cases of dyslipidemia from a normotensive, non-diabetes mellitus population and 1822 non-dyslipidemia subjects in a stage I study. In a follow-up stage II study, we included a larger sample of 3124 controls and 1679 cases with dyslipidemia. Finally, we explored the potential molecular mechanism for the SNP associations using molecular modeling analysis.ResultsWe found a significant association between SNP rs2228570 and dyslipidemia in the additive (adjusted odds ratio (OR) = 1.255, 95% Confidence Interval (CI) = (1.118-1.409), P < 0.001), dominant (OR = 1.384, 95% CI = 1.384 (1.136-1.6), P = 0.001) and recessive models (OR = 1.356, 95%CI = 1.1-1.671, P = 0.004) in stage I. We further established that the rs2228570 variant was significantly associated with dyslipidemia in the additive (adjusted OR = 1.146, 95% CI = 1.053-1247, P = 0.002), dominant (OR = 1.184, 95%CI =1.018-1.376, P = 0.028) and recessive models (OR = 1.209, 95%CI = 1.064-1.374, P = 0.004) in stage II. The TT genotype was significantly higher (4.93 ± 0.75 mmol/L) compared to the TC (4.67 ± 0.47 mmol/L) or CC (4.66 ± 0.44 mmol/L) genotype (P = 0.01) in cases with elevated low-density lipoprotein cholesterol (LDL-C) levels. In contrast, the cases with the TT genotype had significantly lower serum 25(OH)D levels (18.43 ± 5.04 ng/ mL) compared to the TC (26.24 ± 4.16 ng/mL) and CC (36.76 ± 8.10 ng/ mL) genotypes (P < 0.001). Multivariable linear regression analysis indicated that the rs2228750 genotype significantly correlated with serum low-density lipoprotein-C (LDL-C) levels in cases with dyslipidemia. Using molecular modeling analysis, we further found that the rs2228570 variant changed the structure and the stability of VDR and altered the binding energy of its ligand.ConclusionsThe VDR rs2228570 variant may increase susceptibility to dyslipidemia in the Chinese Han population.

Project description:BackgroundSome epidemiological, genetic, and experimental data suggest a possible role of vitamin D in the pathogenesis of multiple sclerosis (MS) and in experimental autoimmune encephalomyelitis. Data on the possible contribution of several single nucleotide polymorphisms (SNP) in the vitamin D receptor (VDR) gene to the risk for MS are controversial. Several studies suggested an interaction between some SNPs in the VDR gene and HLADRB1*1501 in the risk for MS.ObjectivesThe aim of this study was to investigate a possible influence of the SNPs rs2228570 and rs731236 in the VDR gene in the risk for MS. A secondary objective was to address the possible interactions between VDR genes and HLADRB1*1501.MethodsWe analyzed the allelic and genotype frequency of VDR rs2228570, rs731236, and HLADRB1*1501 (rs3135388) in 303 patients with MS and 310 healthy controls, using TaqMan Assays. We also conducted a meta-analysis, that was carried out by using the software Meta-Disc 1.1.1 (http://www.hrc.es/investigacion/metadisc.html; Unit of Clinical Statistics, Hospital Ramón y Cajal, Madrid, Spain). Heterogeneity between studies in terms of degree of association was tested using the Q-statistic.ResultsVDR rs2228570 and rs731236 allelic and genotype frequencies did not differ significantly between MS patients and controls, and were unrelated with the age of onset of MS, gender, and course of MS. HLADRB1*1501 showed a high association with the risk of developing MS 4.76(95% C.I. ?=?3.14-7.27; p<0.0001). The meta-analysis, after excluding data of one study that was responsible of heterogeneity for rs731236 polymorphism, showed lack of relation of both SNPs with the risk for MS. HLADRB1*1501 showed lack of interaction with VDR rs2228570 and rs731236 in increasing MS risk.ConclusionsThese results suggest that VDR rs2228570 and rs731236 polymorphisms are not related with the risk for MS, and did not confirm interaction between these VDR SNPs and HLADRB1 in the risk for MS.

Dataset Information

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.

Purpose

Methods

Results

Conclusion

Publications

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.

Similar Datasets

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