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.
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
VL - 84
SP - 123
EP - 133
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 2
ER -