title: Genetic determinants of macular pigments in women of the Carotenoids in Age-Related Eye Disease Study.
abstract: OBJECTIVE
  To investigate genetic determinants of macular pigment optical density in women from the Carotenoids in Age-Related Eye Disease Study (CAREDS), an ancillary study of the Women's Health Initiative Observational Study.
  
  
  METHODS
  1585 of 2005 CAREDS participants had macular pigment optical density (MPOD) measured noninvasively using customized heterochromatic flicker photometry and blood samples genotyped for 440 single nucleotide polymorphisms (SNPs) in 26 candidate genes related to absorption, transport, binding, and cleavage of carotenoids directly, or via lipid transport. SNPs were individually tested for associations with MPOD using least-squares linear regression.
  
  
  RESULTS
  Twenty-one SNPs from 11 genes were associated with MPOD (P ≤ 0.05) after adjusting for dietary intake of lutein and zeaxanthin. This includes variants in or near genes related to zeaxanthin binding in the macula (GSTP1), carotenoid cleavage (BCMO1), cholesterol transport or uptake (SCARB1, ABCA1, ABCG5, and LIPC), long-chain omega-3 fatty acid status (ELOVL2, FADS1, and FADS2), and various maculopathies (ALDH3A2 and RPE65). The strongest association was for rs11645428 near BCMO1 (βA = 0.029, P = 2.2 × 10(-4)). Conditional modeling within genes and further adjustment for other predictors of MPOD, including waist circumference, diabetes, and dietary intake of fiber, resulted in 13 SNPs from 10 genes maintaining independent association with MPOD. Variation in these single gene polymorphisms accounted for 5% of the variability in MPOD (P = 3.5 × 10(-11)).
  
  
  CONCLUSIONS
  Our results support that MPOD is a multi-factorial phenotype associated with variation in genes related to carotenoid transport, uptake, and metabolism, independent of known dietary and health influences on MPOD.
authors: Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53726, USA.
authors: Kristin J
authors: KJ
authors: Meyers
authors: Elizabeth J
authors: EJ
authors: Johnson
authors: Paul S
authors: PS
authors: Bernstein
authors: Sudha K
authors: SK
authors: Iyengar
authors: Corinne D
authors: CD
authors: Engelman
authors: Chitra K
authors: CK
authors: Karki
authors: Zhe
authors: Z
authors: Liu
authors: Robert P
authors: RP
authors: Igo
authors: Barbara
authors: B
authors: Truitt
authors: Michael L
authors: ML
authors: Klein
authors: D Max
authors: DM
authors: Snodderly
authors: Barbara A
authors: BA
authors: Blodi
authors: Karen M
authors: KM
authors: Gehrs
authors: Gloria E
authors: GE
authors: Sarto
authors: Robert B
authors: RB
authors: Wallace
authors: Jennifer
authors: J
authors: Robinson
authors: Erin S
authors: ES
authors: LeBlanc
authors: Gregory
authors: G
authors: Hageman
authors: Lesley
authors: L
authors: Tinker
authors: Julie A
authors: JA
authors: Mares
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology; D002338:Carotenoids / Q000235:genetics* / Q000378:metabolism; D003430:Cross-Sectional Studies; D000090943:Delta-5 Fatty Acid Desaturase; D005260:Female; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause; D012168:Retinal Pigments / Q000235:genetics* / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000235:genetics; D050559:beta-Carotene 15,15'-Monooxygenase / Q000235:genetics
chemical_list: D000090943:Delta-5 Fatty Acid Desaturase; D012168:Retinal Pigments; D051122:Scavenger Receptors, Class B; D002338:Carotenoids; C000716847:FADS1 protein, human; D050559:beta-Carotene 15,15'-Monooxygenase
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