Environmental, personal, and genetic determinants of response to vitamin D supplementation in older adults.
OBJECTIVE
Suboptimal vitamin D status can be corrected by vitamin D supplementation, but individual responses to supplementation vary. We aimed to examine genetic and nongenetic determinants of change in serum 25-hydroxyvitamin D (25(OH)D) after supplementation.


METHODS
We used data from a pilot randomized controlled trial in which 644 adults aged 60 to 84 years were randomly assigned to monthly doses of placebo, 30 000 IU, or 60 000 IU vitamin D3 for 12 months. Baseline characteristics were obtained from a self-administered questionnaire. Eighty-eight single-nucleotide polymorphisms (SNPs) in 41 candidate genes were genotyped using Sequenom MassArray technology. Serum 25(OH)D levels before and after the intervention were measured using the Diasorin Liaison platform immunoassay. We used linear regression models to examine associations between genetic and nongenetic factors and change in serum 25(OH)D levels.


RESULTS
Supplement dose and baseline 25(OH)D level explained 24% of the variability in response to supplementation. Body mass index, self-reported health status, and ambient UV radiation made a small additional contribution. SNPs in CYP2R1, IRF4, MC1R, CYP27B1, VDR, TYRP1, MCM6, and HERC2 were associated with change in 25(OH)D level, although only CYP2R1 was significant after adjustment for multiple testing. Models including SNPs explained a similar proportion of variability in response to supplementation as models that included personal and environmental factors.


CONCLUSIONS
Stepwise regression analyses suggest that genetic variability may be associated with response to supplementation, perhaps suggesting that some people might need higher doses to reach optimal 25(OH)D levels or that there is variability in the physiologically normal level of 25(OH)D.
Population Health Division (M.W., B.T., C.B., C.H., P.M.W., D.C.W., R.E.N.), QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia; Centre for Research Excellence in Sun and Health (B.T., P.R.E., M.G.K., D.C.W., R.E.N.), Kelvin Grove, Queensland 4059, Australia; Sydney School of Public Health, The University of Sydney (B.K.A.), Sydney, New South Wales 2006, Australia; NorthWest Academic Centre, The University of Melbourne (P.R.E.), St Albans, Victoria 3021, Australia; Melbourne School of Population and Global Health (D.R.E.), The University of Melbourne, Melbourne, Victoria 3010, Australia; Cancer Epidemiology Centre (D.R.E.), Cancer Council Victoria, Melbourne, Victoria 3004, Australia; National Health and Medical Research Council Clinical Trials Centre (V.G.), Sydney Medical School, The University of Sydney, Sydney, New South Wales 2006, Australia; AusSun Research Laboratory (M.G.K.), Queensland University of Technology, Kelvin Grove, Queensland 4059, Australia; and National Centre for Epidemiology and Population Health (R.M.L.), The Australian National University, Canberra, Australian Capital Territory 0200, Australia; and Menzies Research Institute (A.V.), Hobart, Tasmania 7000, Australia.
Mary
M
Waterhouse
Bich
B
Tran
Bruce K
BK
Armstrong
Catherine
C
Baxter
Peter R
PR
Ebeling
Dallas R
DR
English
Val
V
Gebski
Christine
C
Hill
Michael G
MG
Kimlin
Robyn M
RM
Lucas
Alison
A
Venn
Penelope M
PM
Webb
David C
DC
Whiteman
Rachel E
RE
Neale
D000368:Aged; D000369:Aged, 80 and over; D001315:Australia; D054316:Biomarkers, Pharmacological; D019587:Dietary Supplements; D004777:Environment; D005260:Female; D056726:Genetic Association Studies; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome; D014807:Vitamin D / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood; D014808:Vitamin D Deficiency / Q000188:drug therapy* / Q000235:genetics*
D054316:Biomarkers, Pharmacological; D005819:Genetic Markers; D014807:Vitamin D; C104450:25-hydroxyvitamin D