FRIDAY, Aug. 27 (HealthDay News) -- Vitamin D receptor (VDR) binding sites are significantly enriched at genes that have been linked to several autoimmune diseases and cancer, suggesting that vitamin D deficiency may be linked to disease pathogenesis, according to research published online Aug. 24 in Genome Research.
Sreeram V. Ramagopalan, Ph.D., of the University of Oxford in the United Kingdom, and colleagues used the technique called chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq) to isolate fragments of genomic DNA bound to the VDR before and after treatment with calcitriol (the active form of vitamin D). The researchers then mapped the DNA fragments to identify sites of VDR binding, and correlated those sites to disease-associated regions previously identified in genome-wide association studies.
The researchers identified 2,776 sites of VDR binding and 229 genes with significant changes in expression in response to vitamin D. VDR binding sites were significantly enriched near cancer and autoimmune-associated genes, including sites associated with multiple sclerosis, type 1 diabetes, Crohn's disease, systemic lupus erythematosus, rheumatoid arthritis, chronic lymphocytic leukemia, and colorectal cancer.
"The challenge now for researchers is to define the molecular mechanisms through which these variants operate. We show here how ChIP-seq for a biologically important nuclear receptor, integrated with the wealth of genome-wide association studies data now available, provides a powerful approach to further understand the molecular basis of complex disease," the authors write.
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