TY - JOUR
T1 - Common variation in the β-carotene 15,15′-monooxygenase 1 gene affects circulating levels of carotenoids
T2 - A genome-wide association study
AU - Ferrucci, Luigi
AU - Perry, John R.B.
AU - Matteini, Amy
AU - Perola, Markus
AU - Tanaka, Toshiko
AU - Silander, Kaisa
AU - Rice, Neil
AU - Melzer, David
AU - Murray, Anna
AU - Cluett, Christie
AU - Fried, Linda P.
AU - Albanes, Demetrius
AU - Corsi, Anna Maria
AU - Cherubini, Antonio
AU - Guralnik, Jack
AU - Bandinelli, Stefania
AU - Singleton, Andrew
AU - Virtamo, Jarmo
AU - Walston, Jeremy
AU - Semba, Richard D.
AU - Frayling, Timothy M.
N1 - Funding Information:
The InCHIANTI study was supported as a “targeted project” (ICS110.1\RS97.71) by the Italian Ministry of Health and in part by the National Institute on Aging (contracts N01-AG-916413, N01-AG-821336). The ATBC study was supported by the US Public Health Service contracts N01-CN-45165, N01-RC-45035, and N01-RC-37004 from the National Cancer Institute, Department of Health and Human Service. This research was supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. A portion of that support was through an R&D contract with the MedStar Research Institute. We would like to thank Dr. Arun Barua (Iowa State University) for precious help in interpreting our findings in the context of carotenoid metabolism in humans. We acknowledge the important contribution of Leena Peltonen Palotie of the Finnish Public Health Institute, who made genotyping the ATBC study possible. The WHAS was supported by a MERIT AWARD from the National Institute on Aging, Pathogenesis of Physical Disability in Aging Women (R37 AG19905 and R01 AG027012) and the Johns Hopkins Claude D. Pepper Older Americans Independence Center (P30 AG021334).
PY - 2008/8/8
Y1 - 2008/8/8
N2 - 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.
AB - 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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U2 - 10.1016/j.ajhg.2008.12.019
DO - 10.1016/j.ajhg.2008.12.019
M3 - Article
C2 - 19185284
AN - SCOPUS:62649145645
SN - 0002-9297
VL - 84
SP - 123
EP - 133
JO - American journal of human genetics
JF - American journal of human genetics
IS - 2
ER -