How does vitamin E intake correlate with concentrations of tocopherols and their metabolites? Genetic variants involved in interindividual variability in vitamin E bioavailability

Purpose Vitamin E (VE) is essential for human health and may play a role in the aetiology of cardiovascular diseases. However, its absorption efficiency is widely variable. This high interindividual variability is assumed to be due to both dietary and genetic factors. Several polymorphisms have been identified but existing studies have so far focused on single SNPs that only explained a minor fraction of the variability of such a complex phenotype. This study thus aimed to identify a combination of SNPs that could explain a significant part of the variability in VE bioavailability. Methods Thirty-eight healthy male volunteers consumed a meal containing a VE supplement (134 mg a-tocopheryl acetate). Volunteers were genotyped using whole-genome microarrays. a-tocopherol (TOL) concentration was measured in plasma chylomicrons (CM) isolated at regular time intervals over 8 h postprandially. The association of SNPs in or near candidate genes (59 genes representing 4475 SNPs) with the postprandial CM TOL response was assessed by partial least squares regression. Results The postprandial CM TOL response to the meal was highly variable (CV of 81%). Data obtained allowed us to generate a validated significant model (P=1.8.10-8) that included 28 SNPs in 11 genes (ABCA1, ABCG1, APOB, BET1, IRS1, LIPC, NAT2, PNLIP, SLC10A2, SREBF2, ZNF664). This model explained 82% of the variance and allowed us to accurately predict a subject’s VE absorption (Spearman Rho=85% between the measured and predicted VE response). For all these SNPs, univariate analysis showed that subjects who bore different genotypes exhibited a significantly different VE absorption. Conclusions The ability to respond to VE appears to be at least in part genetically determined. A combination of SNPs in 11 genes related to both VE and CM metabolism can explain a large part of the variability in VE absorption in males. These results could allow a better design of future clinical trials aiming at studying the association of VE supplementation with the prevention of cardiovascular diseases.