Journal
AMERICAN JOURNAL OF CLINICAL NUTRITION
Volume 96, Issue 6, Pages 1379-1389Publisher
AMER SOC NUTRITION-ASN
DOI: 10.3945/ajcn.112.034934
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Funding
- NIH [P01 CA087969, 5 U01 HG004399, 5 R01 HL035464, 5 P01 DK070756, 5 T32 CA09001]
- NCI's Cancer Genetic Markers of Susceptibility Study
- Merck Research Laboratories
- [P01 CA87969]
- [R01 CA 131218]
- [U01 CA098233]
- [R03 CA 133937]
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Background: Carotenoids have been hypothesized to reduce the risk of many diseases, but associations with intakes or blood concentrations may arise from other constituents of fruit and vegetables. Use of genetic variation in beta-carotene 15.15' -monooxygenase 1 (BCMO1), a key enzyme in provitamin A carotenoid metabolism, as a surrogate for carotenoid exposure may aid in determining the role of carotenoids unconfounded by other carotenoid-containing food constituents, but important variants must be identified. Objective: Our goal was to select BCMO1 single nucleotide polymorphisms (SNPs) that predict plasma carotenoid concentrations for use in future epidemiologic studies. Design: We assessed the associations between 224 SNPs in BCMO1 +/- 20 kb imputed from the 1000 Genomes Project EUR reference panel with plasma carotenoid and retinol concentrations by using 7 case-control data sets (n = 2344) within the Nurses' Health Study, randomly divided into training (n = 1563) and testing (n = 781) data sets. SNPs were chosen in the training data set through stepwise selection in multivariate linear regression models; beta-coefficients were used as weights in weighted gene scores. Results: Two or 3 SNPs were selected as predictors of beta-carotene, alpha-carotene, beta-cryptoxanthin, and luteinkeaxanthin. In the testing data set, the weighted acne scores were significantly associated with plasma concentrations of the corresponding carotenoid (P = 6.4 X 10(-12), 3.3 x 10(-3), 0.02, and 1.8 X 10(-17), respectively), and concentrations differed by 48%, 15%, 15%, and 36%, respectively, across extreme score quintiles. Conclusions: SNPs in BCMO1 are associated with plasma carotenoid concentrations. Given adequate sample size, the gene scores may be useful surrogates for carotenoid exposure in future studies. Am J Clin Nutr 2012;96:1379-89.
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