Common Variation in the β-Carotene 15,15'-Monooxygénase 1 Gene Affects Circulating Levels of Carotenoids: A Genome-wide Association Study.

Low plasma levels of carotenoids and tocopherols are associated with increased risk of chronic disease and disability. Because dietary intake of these lipid-soluble antioxidant vitamins is only poorly correlated with plasma levels, we hypothesized that circulating carotenoids (vitamin A-related compounds) and tocopherols (vitamin E-related compounds) are affected by common genetic variation. By conducting a genome-wide association study in a sample of Italians (n = 1190), we identified novel common variants associated with circulating carotenoid levels and known lipid variants associated with α-tocopherol levels. Effects were replicated in the Women's Health and Aging Study (n = 615) and in the α-Tocopherol, β-Carotene Cancer Prevention (ATBC) study (n = 2136). In meta-analyses including all three studies, the G allele at rs6564851, near the β-carotene 15,15'-monooxygenase 1 (BCMO1) gene, was associated with higher n-carotene (p = 1.6 x 10-24) and a-carotene (p = 0.0001) levels and lower lycopene (0.003), zeaxanthin (p = 1.3 x 10-5), and lutein (p = 7.3 x 10-15) levels, with effect sizes ranging from 0.10-0.28 SDs per allele. Interestingly, this genetic variant had no significant effect on plasma retinol (p > 0.05). The SNP rs12272004, in linkage disequilibrium with the S19W variant in the APOAS gene, was associated with α-tocopherol (meta-analysis p = 7.8 x 10-10) levels, and this association was substantially weaker when we adjusted for triglyceride levels (p = 0.002). Our findings might shed light on the controversial relationship between lipid-soluble anti-oxidant nutrients and human health. [ABSTRACT FROM AUTHOR]