title: Genetic variants in CYP2R1, CYP24A1, and VDR modify the efficacy of vitamin D3 supplementation for increasing serum 25-hydroxyvitamin D levels in a randomized controlled trial.
abstract: BACKGROUND
  Adequate serum 25-hydroxyvitamin D concentrations, [25(OH)D], are required for optimal bone health, and low levels are associated with chronic diseases.
  
  
  OBJECTIVE
  We investigated whether 41 candidate single nucleotide polymorphisms (SNPs) in vitamin D and calcium pathway genes (GC, DHCR7, CYP2R1, CYP27B1, CYP24A1, VDR, and CASR) are associated with [25(OH)D] or modify the increase in [25(OH)D] from vitamin D3 supplementation.
  
  
  METHODS
  Baseline and year 1 [25(OH)D] measurements from a randomized controlled trial conducted at 11 clinical centers in the United States.
  
  
  METHODS
  A total of 1787 healthy non-Hispanic white participants aged 45-75 years.
  
  
  METHODS
  Vitamin D3 (1000 IU/d), calcium carbonate (1200 mg/d elemental), both, or placebo.
  
  
  METHODS
  Genotype main effects and interactions with vitamin D3 treatment estimated using multiple linear regression.
  
  
  RESULTS
  The baseline serum [25(OH)D] was 25.4 ± 8.7 ng/mL (mean ± SD). Associations with baseline levels were discovered for SNPs in CYP24A1 (rs2209314, rs2762939) and confirmed for SNPs in GC and CYP2R1. After 1 year, [25(OH)D] increased on average by 6.1 ± 8.9 ng/mL on vitamin D3 treatment and decreased by 1.1 ± 8.4 ng/mL on placebo. The increase in [25(OH)D] due to vitamin D3 supplementation was modified by genotypes at rs10766197 near CYP2R1, rs6013897 near CYP24A1, and rs7968585 near VDR.
  
  
  CONCLUSIONS
  The increase in [25(OH)D] attributable to vitamin D3 supplementation may vary according to common genetic differences in vitamin D 25-hydroxylase (CYP2R1), 24-hydroxylase (CYP24A1), and the vitamin D receptor (VDR) genes. These findings have implications for achieving optimal vitamin D status and potentially for vitamin D-related health outcomes.
authors: Departments of Community and Family Medicine (E.L.B., J.R.R., L.A.M., C.I.A., J.A.B.), Genetics (C.I.A.), and Medicine (J.A.B.), Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire 03766; Division of Health and Social Care Research (J.L.P.), and National Institute for Health Research Biomedical Research Centre at Guy's and St Thomas' National Health Service Foundation Trust (J.L.P.), King's College London, London SE1 3QD, United Kingdom; Department of Epidemiology (R.M.B.), Rollins School of Public Health, Emory University, Atlanta, Georgia 30306; Department of Preventive Medicine (J.C.F.), Keck School of Medicine, University of Southern California, Los Angeles, California 90089; Denver Department of Veterans Affairs Medical Center and University of Colorado School of Medicine (D.J.A.), Denver, Colorado 80220; Department of Gastroenterology, Hepatology, and Nutrition (R.S.B.), University of Texas MD Anderson Cancer Center, Houston, Texas 77030; Department of Gastroenterology and Hepatology (C.A.B.), Cleveland Clinic, Cleveland, Ohio 44195; and Department of Medicine (J.A.B.), University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599.
authors: Elizabeth L
authors: EL
authors: Barry
authors: Judy R
authors: JR
authors: Rees
authors: Janet L
authors: JL
authors: Peacock
authors: Leila A
authors: LA
authors: Mott
authors: Christopher I
authors: CI
authors: Amos
authors: Roberd M
authors: RM
authors: Bostick
authors: Jane C
authors: JC
authors: Figueiredo
authors: Dennis J
authors: DJ
authors: Ahnen
authors: Robert S
authors: RS
authors: Bresalier
authors: Carol A
authors: CA
authors: Burke
authors: John A
authors: JA
authors: Baron
mesh_terms: D000368:Aged; D002119:Calcium Carbonate / Q000627:therapeutic use; D002762:Cholecalciferol / Q000627:therapeutic use*; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics*; D000072467:Cytochrome P450 Family 2; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics*; D016896:Treatment Outcome; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014808:Vitamin D Deficiency / Q000188:drug therapy / Q000235:genetics*; D065668:Vitamin D3 24-Hydroxylase / Q000235:genetics*
chemical_list: D018167:Receptors, Calcitriol; C579457:VDR protein, human; D014807:Vitamin D; D002762:Cholecalciferol; C104450:25-hydroxyvitamin D; D000072467:Cytochrome P450 Family 2; C506833:CYP2R1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D002119:Calcium Carbonate