Polymorphisms in the Vitamin D System and Health
Vitamin D, which is essential in calcium metabolism, is produced in the skin after sun
exposure or obtained from food, mainly fatty fish or vitamin D supplements. For activation
vitamin D must be hydroxylated in the liver to 25(OH)D and thereafter in the kidney to
1,25(OH)2D. In the circulation 25(OH)D and 1,25(OH)2D are bound to a carrier protein (DBP),
and for 1,25(OH)2D to exert its effect it has to bind to the vitamin D receptor (VDR).
The serum level of 25(OH)D, which is the metabolite used to evaluate a person's vitamin D
status, is in part genetically determined and several polymorphisms with effects on serum
25(OH)D have been identified. These polymorphisms, where the minor allele frequencies vary
between 16 and 40 %, appear as important for the serum 25(OH)D level as the effect of
season, physical activity or vitamin D supplementation.
Vitamin D is not only vital for the skeleton, but appears to be related to a number of
health outcomes, including mortality as previously demonstrated in the Tromsø study.
However, as the serum level of 25(OH)D is strongly influenced by life-style factors that are
also related to health outcomes, it is difficult to decide whether the relation between
vitamin D and health is causal or not.
On the other hand, the polymorphisms are not influenced by life-style, and the effect of the
polymorphisms will be life-long. Accordingly, they may be a better marker of vitamin D
status than a single serum 25(OH)D measurement. Furthermore, there are a number of
polymorphisms regarding the vitamin D receptor (VDR) that may be associated with health.
In the present study we will therefore relate the polymorphisms affecting the serum 25(OH)D
level and the function of the VDR, with anthropometric and biochemical measures, mortality,
diseases and risk factors for disease. DNA will be obtained from the 4th Tromsø study.
If we find the expected associations between the polymorphisms and diseases, this will
further strengthen the role of vitamin D in human health, and may be important for
recommendations regarding vitamin D supplementation. Considering the high prevalence of
vitamin D deficiency world wide, this may potentially have huge consequences for public
The main purpose of the present study is the vitamin D system, but in the Tromsø study we
have previously also found a number of associations between thyroid and androgen function
and health. Obtaining DNA for analysis will be the major cost in the project, whereas
analyses of individual polymorphisms are relatively cheap. We will therefore also include
polymorphisms regarding thyroid and androgen function.
Time Perspective: Retrospective
Rolf Jorde, Professor
University of Tromso
Norway:National Committee for Medical and Health Research Ethics