Both vitamin E (VE) consumption and blood VE status have been negatively associated with the incidence of degenerative diseases and some cancers. However, the response to VE supplementation is very variable among individuals. This could be due to interindividual variability in VE bioavailability, due, at least partly, to genetic variations in genes involved in VE metabolism. Thus, the main objective was to identify single nucleotide polymorphisms (SNPs) that may be involved in the interindividual variability in α-tocopherol (TOL) bioavailability. The postprandial chylomicron (CM) TOL response (area under the curve of the postprandial CM TOL concentration) to a TOL-rich meal was highly variable (coefficient of variation=81%; n=38). This response was positively correlated with the fasting plasma TOL concentration (r=0.5, p=0.004). A significant (p=1.8×10(-8)) partial least-squares regression model, which included 28 SNPs in 11 genes, explained 82% of this response. First evidence that the interindividual variability in TOL bioavailability is, at least partly, modulated by a combination of SNPs. TOL bioavailability is, at least partly, modulated by genetic variations that can affect long-term TOL status. This allows us to propose a new hypothesis that links the biological response to VE supplementation with one's individual genetic characteristics.