A Combination of Single-Nucleotide Polymorphisms Is Associated with Interindividual Variability in Dietary β-Carotene Bioavailability in Healthy Men

Background: The bioavailability of beta-carotene, the main dietary provitamin A carotenoid, varies among individuals. It is not known whether this variability can affect long-term beta-carotene, and hence vitamin A, status. Objectives: We hypothesized that variations in genes involved in beta-carotene absorption and postprandial metabolism could at least partially explain the high interindividual variability in beta-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 beta-carotene. The postprandial plasma chylomicron beta-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 beta-carotene response (incremental beta-carotene area-under-the-curve concentration over 8 h in chylomicrons). Results: The postprandial chylomicron beta-carotene response was highly variable (CV = 105%) and was positively correlated with the fasting plasma beta-carotene concentration (r = 0.78; P < 0.0001). A significant (P = 6.54 x 10(-3)) multivalidated PLS regression model, which included 25 SNPs in 12 genes, explained 69% of the variance in the postprandial chylomicron beta-carotene response, i.e., beta-carotene bioavailability. Conclusions: Interindividual variability in beta-carotene bioavailability appears to be partially modulated by a combination of SNPs in 12 genes. This variability likely affects the long-term blood beta-carotene status. A theoretic calculation of beta-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 beta-carotene. This trial was registered at clinicaltrials.gov as NCT02100774.