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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
Author(s) -
GaffneyStomberg Erin,
Lutz Laura J,
Shcherbina Anna,
Ricke Darrell O,
Petrovick Martha,
Cropper Thomas L,
Cable Sonya J,
McClung James P
Publication year - 2017
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.3008
Subject(s) - calcitriol receptor , vitamin d and neurology , medicine , single nucleotide polymorphism , endocrinology , parathyroid hormone , placebo , vitamin d deficiency , bone remodeling , snp , vitamin , genotype , calcium , biology , genetics , gene , pathology , alternative medicine
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 D 3 (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.