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Association Between Single Gene Polymorphisms and Bone Biomarkers and Response to Calcium and Vitamin D Supplementation in Young Adults Undergoing Military Training.
Gaffney-Stomberg, E, Lutz, LJ, Shcherbina, A, Ricke, DO, Petrovick, M, Cropper, TL, Cable, SJ, McClung, JP
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2017;32(3):498-507
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Plain language summary
The risk of stress fracture is increased in initial military training (IMT) largely because of unaccustomed activity, resulting in a change in calcium and vitamin D levels. Genetic polymorphisms are variations in a gene that affect the level of gene expression, and bone metabolism and absorption is impacted by this. The primary aim of this randomised, double-blind, placebo controlled trial was to determine whether genes related to Calcium and vitamin D were associated with markers of bone metabolism in 748 young adults entering military training. Participants were randomised to consume bars between meals that were either supplemented with Calcium and vitamin D or placebo that were matched in taste and appearance. Fasting blood samples were taken before and after the 7- to 9-week IMT programme to assess circulating biomarkers and genes. This study found that genetic polymorphisms related to Calcium and vitamin D were associated with vitamin D status and markers of bone metabolism. It also found that genes could predict change in vitamin D absorption levels. Based on these results, the authors conclude this study provides novel insight that helps further understanding between genetics, environment and bone metabolism.
Abstract
Initial military training (IMT) is associated with increased stress fracture risk. In prior studies, supplemental calcium (Ca) and vitamin D provided daily throughout IMT reduced stress fracture incidence, suppressed parathyroid hormone (PTH), and improved measures of bone health compared with placebo. Data were analyzed from a randomized, double-blind, placebo-controlled trial to determine whether single-nucleotide polymorphisms (SNPs) in Ca and vitamin D-related genes were associated with circulating biomarkers of bone metabolism in young adults entering IMT, and whether responses to Ca and vitamin D supplementation were modulated by genotype. Associations between SNPs, including vitamin D receptor (VDR), vitamin D binding protein (DBP), and 1-alpha-hydroxylase (CYP27B1), and circulating biomarkers were measured in fasting blood samples from volunteers (n = 748) starting IMT. Volunteers were block randomized by race and sex to receive Ca (2000 mg) and vitamin D (1000 IU) or placebo daily throughout Army or Air Force IMT (7 to 9 weeks). Total Ca and vitamin D intakes were calculated as the sum of supplemental intake based on intervention compliance and dietary intake. Relationships between SNPs, Ca, and vitamin D intake tertile and change in biomarkers were evaluated in trial completers (n = 391). At baseline, the minor allele of a DBP SNP (rs7041) was positively associated with both 25OHD (B = 4.46, p = 1.97E-10) and 1,25(OH)2 D3 (B = 9.63, p < 0.001). Combined genetic risk score (GRS) for this SNP and a second SNP in the VDR gene (rs1544410) was inversely associated with baseline 25OHD (r = -0.28, p < 0.001) and response to Ca and vitamin D intake differed by GRS (p < 0.05). In addition, presence of the minor allele of a second VDR SNP (rs2228570) was associated with lower P1NP (B = -4.83, p = 0.04) and osteocalcin (B = -0.59, p = 0.03). These data suggest that VDR and DBP SNPs are associated with 25OHD status and bone turnover and those with the highest GRS require the greatest vitamin D intake to improve 25OHD during IMT. © 2016 American Society for Bone and Mineral Research.