title: A Combination of Single-Nucleotide Polymorphisms Is Associated with Interindividual Variability in Cholecalciferol Bioavailability in Healthy Men.
abstract: BACKGROUND
  Most people require dietary vitamin D to achieve the recommended concentration of 25-hydroxyvitamin D [25(OH)D] in the blood. However, the response to vitamin D supplementation is highly variable among individuals.
  
  
  OBJECTIVE
  We assessed whether the variability in cholecalciferol bioavailability was associated with single-nucleotide polymorphisms (SNPs) in candidate genes.
  
  
  METHODS
  In a single-group design, 39 healthy adult men with a mean ± SD age of 33 ± 2 y and mean ± SD body mass index (in kg/m2) of 22.9 ± 0.3 were genotyped with the use of whole-genome microarrays. After an overnight fast, plasma 25(OH)D status was measured, and the subjects then consumed a meal that provided 5 mg cholecalciferol as a supplement. Plasma chylomicron cholecalciferol concentration was measured over 8 h, and cholecalciferol response was assessed by calculating the postprandial area under the curve. Partial least squares regression was used to test the association of SNPs in or near candidate genes (61 genes representing 3791 SNPs) with the postprandial cholecalciferol response.
  
  
  RESULTS
  The postprandial chylomicron cholecalciferol concentration peaked at 5.4 h. The cholecalciferol response was extremely variable among individuals (CV: 47%). It correlated with the chylomicron triglyceride (TG) response (r = 0.60; P < 0.001) but not with the fasting plasma 25(OH)D concentration (r = 0.04; P = 0.83). A significant (P = 1.32 × 10-4) partial least squares regression model that included 17 SNPs in 13 genes (including 5 that have been associated with chylomicron TG response) was associated with the variance in the cholecalciferol response.
  
  
  CONCLUSIONS
  In healthy men, there is a high interindividual variability in cholecalciferol bioavailability that is associated with a combination of SNPs located in or near genes involved in both vitamin D and lipid metabolism. This trial was registered at clinicaltrials.gov as NCT02100774.
authors: NORT Nutrition Obesity and Thrombotic Risk, Aix-Marseille University, INRA National Institute for Agricultural Research, INSERM National Institute of Health and Medical Research, Marseille, France.
authors: Charles
authors: C
authors: Desmarchelier
authors: NORT Nutrition Obesity and Thrombotic Risk, Aix-Marseille University, INRA National Institute for Agricultural Research, INSERM National Institute of Health and Medical Research, Marseille, France; patrick.borel@univ-amu.fr.
authors: Patrick
authors: http://orcid.org/0000-0001-9977-3238
authors: P
authors: Borel
authors: Clinical Investigation Centre, North Hospital, Marseille, France.
authors: Aurélie
authors: A
authors: Goncalves
authors: National Institute for Agricultural Research, Avignon, France.|Security and Quality of Plant Products, University of Avignon, Avignon, France.
authors: Rachel
authors: R
authors: Kopec
authors: NORT Nutrition Obesity and Thrombotic Risk, Aix-Marseille University, INRA National Institute for Agricultural Research, INSERM National Institute of Health and Medical Research, Marseille, France.
authors: Marion
authors: M
authors: Nowicki
authors: Clinical Investigation Centre, Conception Hospital, Marseille, France; and.
authors: Sophie
authors: S
authors: Morange
authors: Clinical Investigation Centre, North Hospital, Marseille, France.
authors: Nathalie
authors: N
authors: Lesavre
authors: NORT Nutrition Obesity and Thrombotic Risk, Aix-Marseille University, INRA National Institute for Agricultural Research, INSERM National Institute of Health and Medical Research, Marseille, France.
authors: Henri
authors: H
authors: Portugal
authors: NORT Nutrition Obesity and Thrombotic Risk, Aix-Marseille University, INRA National Institute for Agricultural Research, INSERM National Institute of Health and Medical Research, Marseille, France.
authors: Emmanuelle
authors: E
authors: Reboul
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002762:Cholecalciferol / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D005504:Food Analysis; D005838:Genotype; D006801:Humans; D008297:Male; D062407:Meals; D020641:Polymorphism, Single Nucleotide
chemical_list: D002762:Cholecalciferol
keywords: 25-hydroxycholecalciferol; absorption; chylomicrons; dietary lipids; genetic polymorphisms; intestine; kinetics; nutrigenetics; postprandial; vitamin D