Polymorphisms in the vitamin D system and health

I dette prosjektet undersøkte vi sammenhengen mellom genetiske faktorene (polymorfismer) som regulerer nivået av 25-hydroxyvitamin D (25(OH)D) i blodet og harde endepunkter så som hjerte-karsykdom, diabetes, død og brudd. Vi benyttet oss av data fra Tromsøundersøkelsen der genetiske data og endepunkts registre var tilgjengelig. På tross av en stor kohort på 27.000 personer fant vi ingen assosiasjon mellom vitamin D polymorfismer og disse endepunktene. Derimot fant vi at genetiske faktorer var av stor betydning for 25(OH)D responsen på vitamin D tilskudd, hvilket kan ha stor betydning for hvilke råd en skal gi angående slike tilskudd. Videre fant vi at det lagres betydelige mengder av vitamin D i fettvev, noe som trolig er forklaring på hvorfor vitamin D nivået i blodet holder seg rimelig bra om vinteren selv om det da ikke er produksjon av vitamin D i huden.

Vitamin D 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. For 1,25(OH)2D to exe rt its effect it has to bind to the vitamin D receptor (VDR). The serum level of 25(OH)D is in part genetically determined and several polymorphisms with effects on serum 25(OH)D have been identified. These polymorphisms appear as important for the serum 25(OH)D level as the effect of season, or vitamin D supplementation. Vitamin D is not only vital for the skeleton, but appears also to be related to heart disease, diabetes, cancer and mortality. However, as the serum level of 25(OH)D is strongly influ enced 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 t he 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 VDR that may be associated with health. In the Troms ø study DNA is available from almost 27,000 individuals, and end-point registers have been made for fractures, coronary infarction, diabetes, cancer and mortality. In the present study we will therefore relate the polymorphisms affecting the serum 25(OH )D level and the function of the VDR with these end-points with the use of a case-cohort design. 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 im portant 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.