March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Genetic Determinants of Macular Pigment Optical Density in the Carotenoids in Age-Related Eye Diseases Study (CAREDS)
Author Affiliations & Notes
  • Kristin J. Meyers
    Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, Wisconsin
  • Elizabeth J. Johnson
    Jean Mayer USDA Human Nutrition, Research Center on Aging, Tufts University, Boston, Massachusetts
  • Sudha K. Iyengar
    Epidemiology & Biostatistics, Case Western Reserve University, Cleveland, Ohio
  • Robert P. Igo, Jr.
    Epidemiology & Biostatistics, Case Western Reserve University, Cleveland, Ohio
  • Max Snodderly
    Nutritional Sciences, University of Texas at Austin, Austin, Texas
  • Michael L. Klein
    Ophthalmology, Casey Eye Institute-OHSU, Portland, Oregon
  • Paul S. Bernstein
    Ophthal and Visual Sciences, Univ of Utah/Moran Eye Center, Salt Lake City, Utah
  • Amy E. Millen
    Social and Preventive Medicine, University at Buffalo, Buffalo, New York
  • Gregory S. Hageman
    Ophthalmology & Visual Sciences, John Moran Eye Center, Salt Lake City, Utah
  • Julie A. Mares
    Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, Wisconsin
  • Footnotes
    Commercial Relationships  Kristin J. Meyers, None; Elizabeth J. Johnson, Alcon Labs (F); Sudha K. Iyengar, None; Robert P. Igo, Jr., None; Max Snodderly, None; Michael L. Klein, None; Paul S. Bernstein, None; Amy E. Millen, None; Gregory S. Hageman, Alcon Labs (F), Optherion, Inc (I), Sequenom (C); Julie A. Mares, None
  • Footnotes
    Support  NIH DK07665, EY13018, EY16886, EY11600, Research to Prevent Blindness
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 1323. doi:
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      Kristin J. Meyers, Elizabeth J. Johnson, Sudha K. Iyengar, Robert P. Igo, Jr., Max Snodderly, Michael L. Klein, Paul S. Bernstein, Amy E. Millen, Gregory S. Hageman, Julie A. Mares; Genetic Determinants of Macular Pigment Optical Density in the Carotenoids in Age-Related Eye Diseases Study (CAREDS). Invest. Ophthalmol. Vis. Sci. 2012;53(14):1323.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : To investigate genetic determinants of the density of lutein and zeaxanthin in the macula of women from the Carotenoids in Age-Related Eye Disease Study (CAREDS), an ancillary study to the Women’s Health Initiative Observational Study (WHI-OS).

Methods: : Macular pigment optical density (MPOD) at 0.5 degrees from foveal center was measured noninvasively using heterochromatic flicker photometry (2001-2004) in 1,804 post-menopausal women (ages 50-79 years) selected from the Iowa, Wisconsin, and Oregon study centers of the WHI. Blood samples from 1,618 women were genotyped for 320 single nucleotide polymorphisms (SNPs) in 14 candidate genes related to absorption, transport, binding, and cleavage of carotenoids directly, or through lipid transport. Dietary intake of lutein and zeaxanthin in 2001-2004 was estimated using responses to a food frequency questionnaire. SNPs were individually tested for associations with MPOD using least-squares linear regression assuming an additive genetic model and adjusting for age, ancestry via principal components, and dietary intake of lutein and zeaxanthin.

Results: : Six of fourteen genes were associated with MPOD. This includes five SNPs in three genes related to HDL levels or cholesterol transport (ABCA1, ABCG5, LIPC); three SNPs in SCARB1 which encodes a plasma membrane scavenger lipoprotein receptor which has been related to carotenoid uptake; two SNPs in RPE65, which encodes a retinoid binding protein in the retinoid visual cycle; and four SNPs from BCMO1, which encodes a pro-vitamin A carotenoid cleavage enzyme. The strongest relationship was for rs11645428 (βA=0.03, P=3.0x10-4) in BCMO1. The minor allele, A (frequency=34%), conferred higher mean levels of MPOD: mean (standard deviation) MPOD for individuals GG was 0.35 (0.21), AG was 0.36 (0.21) and AA was 0.41 (0.23).

Conclusions: : Variation in genes related to the metabolism or uptake of carotenoids and to lipoprotein trafficking predict inter-individual variation in MPOD in postmenopausal women, independent of dietary intake of lutein and zeaxanthin. Further research must be done in order to understand whether these genetic variants explain, in part, the variation in retinal response to dietary lutein and zeaxanthin and whether these are related to risk for age-related macular degeneration.

Keywords: macular pigment • candidate gene analysis • clinical (human) or epidemiologic studies: risk factor assessment 
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