Common variation in the beta-carotene 15,15'-monooxygenase 1 gene affects circulating levels of carotenoids: a genome-wide association study.

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 alpha-tocopherol levels. Effects were replicated in the Women's Health and Aging Study (n = 615) and in the alpha-Tocopherol, beta-Carotene Cancer Prevention (ATBC) study (n = 2136). In meta-analyses including all three studies, the G allele at rs6564851, near the beta-carotene 15,15'-monooxygenase 1 (BCMO1) gene, was associated with higher beta-carotene (p = 1.6 x 10(-24)) and alpha-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 APOA5 gene, was associated with alpha-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.

• Authors: 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, Timothy M Frayling
• Journal: American journal of human genetics (Am J Hum Genet) Vol. 84 Issue 2 Pg. 123-33 (Feb 2009) ISSN: 1537-6605 [Electronic] United States
• PMID: 19185284 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• beta Carotene
• Carotenoids
• BCO1 protein, human
• beta-Carotene 15,15'-Monooxygenase
• alpha-Tocopherol

Topics

• Carotenoids (blood)
• Genetic Variation
• Genome, Human
• Genome-Wide Association Study
• Humans
• Intestinal Absorption
• Polymorphism, Single Nucleotide
• alpha-Tocopherol (blood, metabolism)
• beta Carotene (blood)
• beta-Carotene 15,15'-Monooxygenase (genetics, metabolism)