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Information on the latest vitamin D news and research.

Find out more information on deficiency, supplementation, sun exposure, and how vitamin D relates to your health.

Gene expression and vitamin D: What’s the link?

Depending on the paper one reads, anywhere from 3% to 10% of the active human genome is directly or indirectly signaled by vitamin D. Some of these genes are well known, such as the tyrosine hydroxylase gene, which seems to have a role in depression, and the renin gene that has a role in hypertension. However, to my knowledge, no one has attempted to see which genes are more or less highly expressed in vitamin D deficiency in a representative sample on the population level.

Doctor Standahl Olsen and colleagues of the University of Tromsø in Norway recently changed this. They took blood from 218 postmenopausal in Norway and measured their vitamin D levels and also did a full-genome microarrays assay on the same blood.

Standahl Olsen K, Rylander C, Brustad M, Aksnes L, Lund E. Plasma 25 hydroxyvitamin D level and blood gene expression profiles: a cross-sectional study of the Norwegian Women and Cancer Post-genome Cohort. Eur J Clin Nutr. 2013 Mar 6.

He then subdivided the women into those with vitamin D levels above 20 ng/ml (n=66) and those below 15 ng/ml (n= 83). The average concentration of 25(OH)D of these women was only 17 ng/ml.

As he did the gene array on blood, most of the genes he looked at had to do with the immune system. He found 26 significantly differentially expressed gene sets, mostly having to do with some aspect of immunity. Interestingly, most of the genes were more expressed in the lower 25(OH)D deficient group than in the higher 25(OH)D group. This is in line with the hypothesis that vitamin D limits pathological immune responses that may ultimately lead to hypersensitivity or autoimmunity. In other words, without vitamin D, the immune system is out of control.

He wrote:

“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. 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.”

Standahl also stated,

“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.”

He concluded:

“We conclude that vitamin D status was associated with pathways related to immune system and immune cell function, as well as major signaling cascades. . . . This study demonstrates the feasibility of blood gene expression profiling to explore effects of nutritional factors such as vitamin D in the general population. Studies using similar methods are likely to yield increased insight into the molecular effects of nutrients.”

In my opinion, in order to fully answer the question he asked, “what genes are differentially expressed in the blood in vitamin D deficiency,” one would need a sample of blood from a group of people severely deficient (<10 ng/ml) and compare it to a group with natural levels (40-50 ng/ml). Perhaps future studies using similar methods will have a population sample that can achieve this.

  About: John Cannell, MD

Dr. John Cannell is founder of the Vitamin D Council. He has written many peer-reviewed papers on vitamin D and speaks frequently across the United States on the subject. Dr. Cannell holds an M.D. and has served the medical field as a general practitioner, emergency physician, and psychiatrist.

3 Responses to Gene expression and vitamin D: What’s the link?

  1. Rita and Misty says:

    It would be awesome if one day (lets say in the next 50 years) the majority of the world had 25(OH)D levels of 40-50 ng/ml.

    A goal to keep us in the Vitamin D Community busy…

  2. roger.rolfe@sympatico.ca says:

    Great blog post. So many people think the genome is a given, rather than a library that environmental factors like vitamin D status can influence the expression of. BTW, you should have used quotes in para. 5 around the phrase “vitamin D limits pathological immune responses…..” since it’s taken directly from Standahl’s article. A small point but an important one.

  3. Matt Rhodes says:

    This study tells one which genes turn off as the deficiency goes from bad to worse. Ideally it needs repeated with a range of vitamin D levels to see which genes turn off for a mild deficiency vs. an increasingly severe deficiency to allow an idea of what processes get shut down or turned on in what order as the levels decline. Possibly one could then come to conclusions about what levels are required to normalize blood pressure or cure an autoimmune disease like lupus as they are not necessarily the same levels. And then again one can just take enough D3 now to bring your levels up to the 50-60 ng/ml range and wait for the science to catch up!