title: β-Carotene 15,15'-monooxygenase 1 single nucleotide polymorphisms in relation to plasma carotenoid and retinol concentrations in women of European descent.
abstract: 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 β-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.
  
  
  METHODS
  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; β-coefficients were used as weights in weighted gene scores.
  
  
  RESULTS
  Two or 3 SNPs were selected as predictors of β-carotene, α-carotene, β-cryptoxanthin, and lutein/zeaxanthin. In the testing data set, the weighted gene scores were significantly associated with plasma concentrations of the corresponding carotenoid (P = 6.4 × 10⁻¹², 3.3 × 10⁻³, 0.02, and 1.8 × 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.
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Hendrickson
authors.forename: Aditi
authors.initials: A
authors.lastname: Hazra
authors.forename: Constance
authors.initials: C
authors.lastname: Chen
authors.forename: A Heather
authors.initials: AH
authors.lastname: Eliassen
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.forename: Bernard A
authors.initials: BA
authors.lastname: Rosner
authors.forename: Walter C
authors.initials: WC
authors.lastname: Willett
mesh_terms: D000328:Adult; D001185:Artificial Intelligence; D015415:Biomarkers / Q000097:blood; D002338:Carotenoids / Q000097:blood*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005819:Genetic Markers; D055106:Genome-Wide Association Study; D006801:Humans; D014975:Lutein / Q000097:blood; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014481:United States; D014801:Vitamin A / Q000097:blood*; D044465:White People; D024341:Xanthophylls / Q000097:blood; D065146:Zeaxanthins; D019207:beta Carotene / Q000097:blood; D050559:beta-Carotene 15,15'-Monooxygenase / Q000235:genetics* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D005819:Genetic Markers; D024341:Xanthophylls; D065146:Zeaxanthins; D019207:beta Carotene; D014801:Vitamin A; D002338:Carotenoids; C041635:alpha-carotene; C493358:BCO1 protein, human; D050559:beta-Carotene 15,15'-Monooxygenase; D014975:Lutein