Polymorphisms in the Vitamin D System and Health
|Study Design:||Time Perspective: Retrospective|
|Official Title:||Polymorphisms in the Vitamin D System and Health|
|Study Start Date:||April 2011|
|Estimated Study Completion Date:||July 2016|
|Estimated Primary Completion Date:||October 2015 (Final data collection date for primary outcome measure)|
subjects with myocardial infarction in the Tromsø study end point registry
type 2 diabetes
subjects with type 2 diabetes in the Tromsø study end point registry
subjects with stroke in the Tromsø study end point registry
subjects with fracture in the Tromsø study end point registry
subjects with cancer in the Tromsø study end point registry
subjects registered as dead in the Tromsø study end point registry
subjects with aortic stenosis in the Tromsø study end point registry
randomly selected controls from the Tromsø study
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01395303
|University of Tromsø|
|Tromsø, Norway, 9037|
|Principal Investigator:||Rolf Jorde, Professor||University of Tromso|