Polymorphisms in the Vitamin D System and Health
Condition: Infarction; Stroke; Diabetes; Fracture; Aortic Stenosis; Cancer; Death
MeSH terms: Aortic Valve Stenosis; Infarction
Study type: Observational

Summary: 
      Polymorphisms in the vitamin D system appear to affect the serum 25(OH)D levels. If so one
      would expect these polymorphisms to be associated with vitamin D related conditions and
      diseases, which will be tested in the present study including DNA analyses in 9700 subjects
    

Detailed description: 
      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
      health.

      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
Sampling method: Probability Sample
Study population: 
        Subjects from the fourth Tromsø study performed in 1994-1995 who had blood samples taken
        for later DNA analyses
      
Biospecimen description: 
      DNA from blood clots
    
Keywords: infarction; stroke; diabetes; fracture; aortic stenosis; cancer; death; vitamin D; androgens; thyroid hormones