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Response to vitamin D related to DBP and CYP2RI genes – Aug 2013

Eur J Endocrinol August 9, 2013 EJE-13-0233
Allan Didriksen allan.didriksen at unn.no.
Guri Grimnes,
Moira Strand Hutchinson,
Marie Kjærgaard,
Johan Svartberg,
Ragnar Martin Joakimsen and
Rolf Jorde
A Didriksen, Insitute of Clinical Medicine, University of Tromsø, Tromsø, Norway
G Grimnes, Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
M Hutchinson, Insitute of Clinical Medicine, University of Tromsø, Tromsø, Norway
M Kjærgaard, Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
J Svartberg, Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
R Joakimsen, Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
R Jorde, Institute of Clinical Medicine, University of Tromsø, Tromsø, 9037, Norway

Objective: The serum 25-hydroxyvitamin D (25(OH)D) level is not only dependent upon vitamin D intake and production in the skin, but also on genetic factors. Thus, in large genome-wide association studies it has been shown that single nucleotide polymorphisms (SNPs) in the vitamin D binding protein (DBP), as well as in enzymes related to activation or degradation of vitamin D and its metabolites, are as important for the serum 25(OH)D level as the effect of season. How these SNPs affect the serum 25(OH)D response to vitamin D supplementation is uncertain.

Design and Methods: Data were pooled from three randomized controlled trials where 40 000 IU vitamin D per week was given for six months. Serum 25(OH)D was measured before and at the end of the intervention, and the subjects were genotyped for SNPs related to the serum 25(OH)D level.

Results: Baseline 25(OH)D levels were significantly related to SNPs in the DBP and CYP2RI genes. Those with SNPs associated with the lowest baseline 25(OH)D levels also had the smallest increase (delta) after supplementation. Those with the lowest baseline serum 25(OH)D (without regard to genotypes) had the highest increase (delta) after supplementation. Subjects with high body mass index (BMI) had the lowest baseline 25(OH)D levels and also the smallest increase (delta) after supplementation.

Conclusions: The serum 25(OH)D response to supplementation depends on genes, baseline level and BMI.
However, whether this is clinically important or not depends on the therapeutic window of vitamin D, an issue that is still not settled.

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