title: A Combination of Single-Nucleotide Polymorphisms Is Associated with Interindividual Variability in Dietary β-Carotene Bioavailability in Healthy Men.
abstract: BACKGROUND
  The bioavailability of β-carotene, the main dietary provitamin A carotenoid, varies among individuals. It is not known whether this variability can affect long-term β-carotene, and hence vitamin A, status.
  
  
  OBJECTIVE
  We hypothesized that variations in genes involved in β-carotene absorption and postprandial metabolism could at least partially explain the high interindividual variability in β-carotene bioavailability. Thus, the main objectives of this study were to identify associated single-nucleotide polymorphisms (SNPs), and to estimate whether populations with different allele frequencies at these SNPs could have different abilities to absorb provitamin A carotenoids.
  
  
  METHODS
  In this single-group design, 33 healthy, nonobese adult men were genotyped with the use of whole-genome microarrays. After an overnight fast, they consumed a test meal containing 100 g tomato puree providing 0.4 mg β-carotene. The postprandial plasma chylomicron β-carotene concentration was then measured at regular time intervals over 8 h. Partial least squares (PLS) regression was used to identify the best combination of SNPs in or near candidate genes (54 genes representing 2172 SNPs) that was associated with the postprandial chylomicron β-carotene response (incremental β-carotene area-under-the-curve concentration over 8 h in chylomicrons).
  
  
  RESULTS
  The postprandial chylomicron β-carotene response was highly variable (CV = 105%) and was positively correlated with the fasting plasma β-carotene concentration (r = 0.78; P < 0.0001). A significant (P = 6.54 × 10(-3)) multivalidated PLS regression model, which included 25 SNPs in 12 genes, explained 69% of the variance in the postprandial chylomicron β-carotene response, i.e., β-carotene bioavailability.
  
  
  CONCLUSIONS
  Interindividual variability in β-carotene bioavailability appears to be partially modulated by a combination of SNPs in 12 genes. This variability likely affects the long-term blood β-carotene status. A theoretic calculation of β-carotene bioavailability in 4 populations of the international HapMap project suggests that populations with different allele frequencies in these SNPs might exhibit a different ability to absorb dietary β-carotene. This trial was registered at clinicaltrials.gov as NCT02100774.
authors.affiliation: French National Institute for Agricultural Research, UMR INRA 1260, Marseille, France; French National Institute of Health and Medical Research, UMR_S 1062, Marseille, France; and Aix-Marseille Université, Nutrition, Obesity and Risk of Thrombosis, Marseille, France Patrick.Borel@univ-amu.fr.
authors.forename: Patrick
authors.identifier: http://orcid.org/0000-0001-9977-3238
authors.initials: P
authors.lastname: Borel
authors.affiliation: French National Institute for Agricultural Research, UMR INRA 1260, Marseille, France; French National Institute of Health and Medical Research, UMR_S 1062, Marseille, France; and Aix-Marseille Université, Nutrition, Obesity and Risk of Thrombosis, Marseille, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Desmarchelier
authors.affiliation: French National Institute for Agricultural Research, UMR INRA 1260, Marseille, France; French National Institute of Health and Medical Research, UMR_S 1062, Marseille, France; and Aix-Marseille Université, Nutrition, Obesity and Risk of Thrombosis, Marseille, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Nowicki
authors.affiliation: French National Institute for Agricultural Research, UMR INRA 1260, Marseille, France; French National Institute of Health and Medical Research, UMR_S 1062, Marseille, France; and Aix-Marseille Université, Nutrition, Obesity and Risk of Thrombosis, Marseille, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Bott
mesh_terms: D000328:Adult; D001682:Biological Availability; D002914:Chylomicrons / Q000097:blood; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D014802:Vitamin A Deficiency / Q000235:genetics; D019207:beta Carotene / Q000378:metabolism*
chemical_list: D002914:Chylomicrons; D019207:beta Carotene
keywords: SNP; absorption; chylomicrons; genetic polymorphisms; genetic variations; nutrigenetics; postprandial metabolism; vitamin A