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

By Luigi Ferrucci, John R.B. Perry, Amy Matteini, Markus Perola, Toshiko Tanaka, Kaisa Silander, Neil Rice, David Melzer, Anna Murray, Christie Cluett, Linda P. Fried, Demetrius Albanes, Anna-Maria Corsi, Antonio Cherubini, Jack Guralnik, Stefania Bandinelli, Andrew Singleton, Jarmo Virtamo, Jeremy Walston, Richard D. Semba and Timothy M. Frayling

Abstract

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 β-carotene (p = 1.6 × 10−24) and α-carotene (p = 0.0001) levels and lower lycopene (0.003), zeaxanthin (p = 1.3 × 10−5), and lutein (p = 7.3 × 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 APOA5 gene, was associated with α-tocopherol (meta-analysis p = 7.8 × 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

Topics: Article
Publisher: Elsevier
OAI identifier: oai:pubmedcentral.nih.gov:2668002
Provided by: PubMed Central
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