Association Between Single Gene Polymorphisms and Bone Biomarkers and Response to Calcium and Vitamin D Supplementation in Young Adults Undergoing Military Training.
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)2D3(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.
United States (US) Army Research Institute of Environmental Medicine, Natick, MA, USA.
Erin
E
Gaffney-Stomberg
United States (US) Army Research Institute of Environmental Medicine, Natick, MA, USA.
Laura J
LJ
Lutz
Massachusetts Institute for Technology Lincoln Laboratory, Lexington, MA, USA.
Anna
A
Shcherbina
Massachusetts Institute for Technology Lincoln Laboratory, Lexington, MA, USA.
Darrell O
DO
Ricke
Massachusetts Institute for Technology Lincoln Laboratory, Lexington, MA, USA.
Martha
M
Petrovick
Lackland Air Force Base, San Antonio, TX, USA.
Thomas L
TL
Cropper
Initial Military Training Center of Excellence, Fort Eustis, VA, USA.
Sonya J
SJ
Cable
United States (US) Army Research Institute of Environmental Medicine, Natick, MA, USA.
James P
JP
McClung
D000886:Anthropometry; D015415:Biomarkers / Q000378:metabolism*; D001842:Bone and Bones / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology*; D003710:Demography; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D008297:Male; D008889:Military Personnel; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology*; D055815:Young Adult
D015415:Biomarkers; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D002118:Calcium
BIOCHEMICAL MARKERS OF BONE TURNOVER; EXERCISE; GENETICS; NUTRITION; PTH/VIT D