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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 |
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| 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 |
| Affiliation: | 1 Longitudinal Studies Section, Clinical Research Branch, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, United States of America 2 Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, United States of America 3 Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, United States of America 4 Genetics of Complex Traits, Institute of Biomedical and Clinical Sciences, Peninsula College of Medicine and Dentistry, University of Exeter, EX1 2LU Devon, United Kingdom 5 Department of Medicine, Division of Geriatrics, Johns Hopkins Medical Institutions, Baltimore, MD 21224, USA 6 FIMM, Department of Molecular Medicine, Institute of Molecular Medicine, and National Public Health Institute, FI-00271 Helsinki, Finland 7 MedStar Research Institute, Baltimore, MD 21225, USA 8 Columbia University, Mailman School of Public Health, New York, NY 10032, USA 9 Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA 10 Tuscany Regional Health Agency, 50100 Florence, Italy 11 Institute of Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, University of Perugia Medical School, 06122 Perugia, Italy 12 Geriatric Unit, Azienda Sanitaria di Firenze, 50125 Florence, Italy 13 Department of Health Promotion and Chronic Disease Prevention, National Public Health Institute, FI-00271 Helsinki, Finland 14 Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA |
| 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. |
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