Role of vitamin D receptor and vitamin D binding protein restriction fragment length polymorphisms in determining dose response to vitamin D: A randomized double blind placebo controlled trial

摘要

Serum 25-hydroxyvitamin D (25OHD) is considered to be the best biomarker of vitamin D status. Besides the dietary intake of vitamin D and exposure to sunlight, there are other factors that affect serum 25OHD such as weight, race, sex, binding protein and the effect of vitamin D receptor (VDR) and vitamin D binding protein (DBP) single nucleotide polymorphisms (SNPs) on serum 25OHD levels.;The primary objective of this study was to determine the effect of genotypes based on VDR and DBP SNPs on the dose response to vitamin D in terms of serum 25OHD and serum parathyroid hormone (PTH).;We used specimens from an ongoing study (ViDOS - vitamin D supplementation in older subjects) - a double blind randomized placebo-controlled trial that enrolled 160 healthy Caucasian postmenopausal women, with vitamin D insufficiency (mean serum 25OHD 15.6 ng/ml) recruited during winter and followed for one year. The subjects were randomly assigned to placebo, vitamin D3 400, 800, 1600, 2400, 3200, 4000 or 4800 IU/d and calcium to increase total calcium intake to 1200-1400 mg/day based on 7-day food diaries. The primary outcomes were serum 25OHD and serum parathyroid hormone (PTH) for this study. Serum 25OHD and PTH were measured by immunoassay. Genotype analysis was performed on DNA isolated from peripheral leucocytes from patients.;There was a significant effect of BMI, baseline serum 25OHD and dose of vitamin D supplementation on final serum 25OHD. However, there was no effect of genotypes based on VDR and DBP SNPs on serum 25OHD at the end of one year after vitamin D supplementation after adjustment for relevant confounders like age, BMI, baseline serum 25OHD, dose, serum creatinine, smoking status, alcohol intake, caffeine intake and calcium intake. This study represents the first longitudinal placebo controlled randomized trial that examined the pharmacogenetics of vitamin D metabolism together with a dose response to vitamin D; these results do not support previous positive association data.