title: Genetic evidence for role of carotenoids in age-related macular degeneration in the Carotenoids in Age-Related Eye Disease Study (CAREDS).
abstract: OBJECTIVE
  We tested variants in genes related to lutein and zeaxanthin status for association with age-related macular degeneration (AMD) in the Carotenoids in Age-Related Eye Disease Study (CAREDS).
  
  
  METHODS
  Of 2005 CAREDS participants, 1663 were graded for AMD from fundus photography and genotyped for 424 single nucleotide polymorphisms (SNPs) from 24 candidate genes for carotenoid status. Of 337 AMD cases 91% had early or intermediate AMD. The SNPs were tested individually for association with AMD using logistic regression. A carotenoid-related genetic risk model was built using backward selection and compared to existing AMD risk factors using the area under the receiver operating characteristic curve (AUC).
  
  
  RESULTS
  A total of 24 variants from five genes (BCMO1, BCO2, NPCL1L1, ABCG8, and FADS2) not previously related to AMD and four genes related to AMD in previous studies (SCARB1, ABCA1, APOE, and ALDH3A2) were associated independently with AMD, after adjusting for age and ancestry. Variants in all genes (not always the identical SNPs) were associated with lutein and zeaxanthin in serum and/or macula, in this or other samples, except for BCO2 and FADS2. A genetic risk score including nine variants significantly (P = 0.002) discriminated between AMD cases and controls beyond age, smoking, CFH Y402H, and ARMS2 A69S. The odds ratio (95% confidence interval) for AMD among women in the highest versus lowest quintile for the risk score was 3.1 (2.0-4.9).
  
  
  CONCLUSIONS
  Variants in genes related to lutein and zeaxanthin status were associated with AMD in CAREDS, adding to the body of evidence supporting a protective role of lutein and zeaxanthin in risk of AMD.
authors.affiliation: Department of Ophthalmology and Visual Sciences, McPherson Eye Research Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
authors.forename: Kristin J
authors.initials: KJ
authors.lastname: Meyers
authors.forename: Julie A
authors.initials: JA
authors.lastname: Mares
authors.forename: Robert P
authors.initials: RP
authors.lastname: Igo
authors.forename: Barbara
authors.initials: B
authors.lastname: Truitt
authors.forename: Zhe
authors.initials: Z
authors.lastname: Liu
authors.forename: Amy E
authors.initials: AE
authors.lastname: Millen
authors.forename: Michael
authors.initials: M
authors.lastname: Klein
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Johnson
authors.forename: Corinne D
authors.initials: CD
authors.lastname: Engelman
authors.forename: Chitra K
authors.initials: CK
authors.lastname: Karki
authors.forename: Barbara
authors.initials: B
authors.lastname: Blodi
authors.forename: Karen
authors.initials: K
authors.lastname: Gehrs
authors.forename: Lesley
authors.initials: L
authors.lastname: Tinker
authors.forename: Robert
authors.initials: R
authors.lastname: Wallace
authors.forename: Jennifer
authors.initials: J
authors.lastname: Robinson
authors.forename: Erin S
authors.initials: ES
authors.lastname: LeBlanc
authors.forename: Gloria
authors.initials: G
authors.lastname: Sarto
authors.forename: Paul S
authors.initials: PS
authors.lastname: Bernstein
authors.forename: John Paul
authors.initials: JP
authors.lastname: SanGiovanni
authors.forename: Sudha K
authors.initials: SK
authors.lastname: Iyengar
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002338:Carotenoids / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D015994:Incidence; D008268:Macular Degeneration / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
chemical_list: D002338:Carotenoids
keywords: carotenoids; genes; macular degeneration