title: 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.affiliation: Longitudinal Studies Section, Clinical Research Branch, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, United States of America. ferruccilu@grc.nia.nih.gov
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: John R B
authors.initials: JR
authors.lastname: Perry
authors.forename: Amy
authors.initials: A
authors.lastname: Matteini
authors.forename: Markus
authors.initials: M
authors.lastname: Perola
authors.forename: Toshiko
authors.initials: T
authors.lastname: Tanaka
authors.forename: Kaisa
authors.initials: K
authors.lastname: Silander
authors.forename: Neil
authors.initials: N
authors.lastname: Rice
authors.forename: David
authors.initials: D
authors.lastname: Melzer
authors.forename: Anna
authors.initials: A
authors.lastname: Murray
authors.forename: Christie
authors.initials: C
authors.lastname: Cluett
authors.forename: Linda P
authors.initials: LP
authors.lastname: Fried
authors.forename: Demetrius
authors.initials: D
authors.lastname: Albanes
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Corsi
authors.forename: Antonio
authors.initials: A
authors.lastname: Cherubini
authors.forename: Jack
authors.initials: J
authors.lastname: Guralnik
authors.forename: Stefania
authors.initials: S
authors.lastname: Bandinelli
authors.forename: Andrew
authors.initials: A
authors.lastname: Singleton
authors.forename: Jarmo
authors.initials: J
authors.lastname: Virtamo
authors.forename: Jeremy
authors.initials: J
authors.lastname: Walston
authors.forename: Richard D
authors.initials: RD
authors.lastname: Semba
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Frayling
mesh_terms: D002338:Carotenoids / Q000097:blood*; D014644:Genetic Variation; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D007408:Intestinal Absorption; D020641:Polymorphism, Single Nucleotide; D024502:alpha-Tocopherol / Q000097:blood* / Q000378:metabolism; D019207:beta Carotene / Q000097:blood; D050559:beta-Carotene 15,15'-Monooxygenase / Q000235:genetics* / Q000378:metabolism
chemical_list: D019207:beta Carotene; D002338:Carotenoids; C493358:BCO1 protein, human; D050559:beta-Carotene 15,15'-Monooxygenase; D024502:alpha-Tocopherol