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Do vitamin D levels influence genes for immune health?

By Stephen DANIELLS , 11-Mar-2013
Last updated on 12-Mar-2013 at 17:22 GMT

Blood levels of vitamin D may affect the expression of genes linked to immune health and inflammation, Norwegian scientists report for the first time.

Data from 218 people indicated that vitamin D levels are linked to “molecular pathways that may ultimately affect the potential onset of diseases”, according to findings published in the European Journal of Clinical Nutrition .

“Overarching gene sets such as signaling in immune system (gene set 27), innate immunity signaling (gene set 30), cytokine production (gene set 52) and chemokine signaling (gene set 49) were differentially expressed according to vitamin D status,” wrote researchers from the University of Tromso.

“The majority of genes in these gene sets were associated with vitamin D deficiency, in line with the hypothesis that vitamin D limits pathological immune responses that may ultimately lead to hypersensitivity or autoimmunity.”

Shining light on the benefits of the sunshine vitamin

Vitamin D refers to two biologically inactive precursors - D3, also known as cholecalciferol, and D2, also known as ergocalciferol.

Both D3 and D2 precursors are transformed in the liver and kidneys into 25- hydroxyvitamin D (25(OH)D), the non-active 'storage' form, and 1,25-dihydroxyvitamin D (1,25(OH)2D), the biologically active form that is tightly controlled by the body.

Vitamin D deficiency in adults is reported to precipitate or exacerbate osteopenia, osteoporosis, muscle weakness, fractures, common cancers, autoimmune diseases, infectious diseases and cardiovascular diseases.

In order to explore the molecular effects of vitamin D, the Norwegian scientists used gene expression technology and collected data from 218 free-living, middle-aged Norwegian women.

Gene expression pathways were compared with vitamin D status in the women, with vitamin D sufficiency defined as 25(OH)D over 50 nmol/l, and deficiency as 25(OH)D below 37.5 nmol/l.

Results showed that vitamin D status was associated with the immune system, the production of cytokines, and chemokine signaling, said the researchers.

Pathways

“Three pathways related to innate immunity were more highly expressed in the vitamin D-deficient group: TLR signaling (gene set 64 and 65), a major pathway governing the inflammatory response to infection, and IL-1R pathway (gene set 55), which increases migration of leukocytes to sites of infection,” wrote the researchers.

In vitro studies have shown that 1,25(OH)2D or vitamin D analogs have anti-inflammatory properties by down-regulating inflammatory gene expression in monocytes/macrophages.”

The researchers also reported a link between CD14 – a pattern recognition receptor for lipopolysaccharides and other pathogen compounds – and several gene sets.

“CD14 […] acts as a co-receptor with TLR4 to trigger cytokine production and inflammatory response to microbial infection. Its association with vitamin D deficiency in our data set is in line with the general anti-inflammatory actions of 1,25(OH)2D.”

The Tromso-based scientists caution that the study shows correlation and not causation, and conclusions are limited to post-menopausal women.

“In the multi-factorial setting of a free-living population, the impact of single nutrients such as vitamin D is not easily detected. Gene expression differences would perhaps be larger if the 25(OH)D concentrations had a wider distribution than in this study population, for example, in an intervention study.”

Despite these limitations, they said the study shows that it is feasible to use blood gene expression profiling to investigate the effects of nutrients in the general population.

Source: European Journal of Clinical Nutrition
Published online ahead of print, doi: 10.1038/ejcn.2013.53
“Plasma 25 hydroxyvitamin D level and blood gene expression profiles: a cross-sectional study of the Norwegian Women and Cancer Post-genome Cohort”
Authors: K.S. Olsen, C. Rylander, M. Brustad, L. Aksnes, E.  Lund

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