ArticleBMC medicine2013
Vitamin D receptor ChIP-seq in primary CD4+ cells: relationship to serum 25-hydroxyvitamin D levels and autoimmune disease.
Article in BMC medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 4 of them syntheses that pooled it.
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Who cites it
36 citing papers in PubMed, 4 syntheses or guidelines pooled it, 70 citations in OpenAlex.
- Pooled it
- Meta-Analysis of Differential Connectivity in Gene Co-Expression Networks in Multiple Sclerosis.International journal of molecular sciences · 2016Pooled it
- Association between vitamin D receptor polymorphisms and multiple sclerosis: systematic review and meta-analysis of case-control studies.Cellular & molecular immunology · 2015Pooled it
- Pooled it
- Genomic profiling of active vitamin D colonic responses in African- and European-Americans identifies an ancestry-related regulatory variant of POLB.PLoS genetics · 2026Article
- Molecular Insight into the Role of Vitamin D in Immune-Mediated Inflammatory Diseases.International journal of molecular sciences · 2025Review
- Calcitriol restrains microglial M1 polarization and alleviates dopaminergic degeneration in hemiparkinsonian mice by boosting regulatory T-cell expansion.Brain and behavior · 2024Article
- Vitamin D status associates with skeletal muscle loss after anterior cruciate ligament reconstruction.JCI insight · 2023Article
- A Single Vitamin DNutrients · 2022Article
- Vitamin D and Its Target Genes.Nutrients · 2022Review
- Prevalence of Vitamin D Deficiency Between Type 2 Diabetes Mellitus Patients and Non-Diabetics in the Arab Gulf.Diabetes, metabolic syndrome and obesity : targets and therapy · 2022Article
- Genomic and epigenomic active vitamin D responses in human colonic organoids.Physiological genomics · 2021Article
- The role of CD4International journal of biological sciences · 2021Review
- Vitamin D and Demyelinating Diseases: Neuromyelitis Optica (NMO) and Multiple Sclerosis (MS).Autoimmune diseases · 2020Review
- Environmental Influencers, MicroRNA, and Multiple Sclerosis.Journal of central nervous system disease · 2020Review
- Environmental exposures and the risk of multiple sclerosis in Saudi Arabia.BMC neurology · 2018Article
- The Vitamin D⁻Folate Hypothesis as an Evolutionary Model for Skin Pigmentation: An Update and Integration of Current Ideas.Nutrients · 2018Review
- Genomic Effects of the Vitamin D Receptor: Potentially the Link between Vitamin D, Immune Cells, and Multiple Sclerosis.Frontiers in immunology · 2018Review
- Optimal vitamin D spurs serotonin: 1,25-dihydroxyvitamin D represses serotonin reuptake transport (Genes & nutrition · 2018Article
- Functional genomics analysis of vitamin D effects on CD4+ T cells in vivo in experimental autoimmune encephalomyelitis .Proceedings of the National Academy of Sciences of the United States of America · 2017Article
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Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundVitamin D insufficiency has been implicated in autoimmunity. ChIP-seq experiments using immune cell lines have shown that vitamin D receptor (VDR) binding sites are enriched near regions of the genome associated with autoimmune diseases. We aimed to investigate VDR binding in primary CD4+ cells from healthy volunteers.
methodsWe extracted CD4+ cells from nine healthy volunteers. Each sample underwent VDR ChIP-seq. Our results were analyzed in relation to published ChIP-seq and RNA-seq data in the Genomic HyperBrowser. We used MEMEChIP for de novo motif discovery. 25-Hydroxyvitamin D levels were measured using liquid chromatography-tandem mass spectrometry and samples were divided into vitamin D sufficient (25(OH)D ≥75 nmol/L) and insufficient/deficient (25(OH)D <75 nmol/L) groups.
resultsWe found that the amount of VDR binding is correlated with the serum level of 25-hydroxyvitamin D (r = 0.92, P= 0.0005). In vivo VDR binding sites are enriched for autoimmune disease associated loci, especially when 25-hydroxyvitamin D levels (25(OH)D) were sufficient (25(OH)D ≥75: 3.13-fold, P<0.0001; 25(OH)D <75: 2.76-fold, P<0.0001; 25(OH)D ≥75 enrichment versus 25(OH)D <75 enrichment: P= 0.0002). VDR binding was also enriched near genes associated specifically with T-regulatory and T-helper cells in the 25(OH)D ≥75 group. MEME ChIP did not identify any VDR-like motifs underlying our VDR ChIP-seq peaks.
conclusionOur results show a direct correlation between in vivo 25-hydroxyvitamin D levels and the number of VDR binding sites, although our sample size is relatively small. Our study further implicates VDR binding as important in gene-environment interactions underlying the development of autoimmunity and provides a biological rationale for 25-hydroxyvitamin D sufficiency being based at 75 nmol/L. Our results also suggest that VDR binding in response to physiological levels of vitamin D occurs predominantly in a VDR motif-independent manner.
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