TY - JOUR
T1 - Genetic determinants of macular pigments in women the carotenoids in age-related eye disease study
AU - Meyers, Kristin J.
AU - Johnson, Elizabeth J.
AU - Bernstein, Paul S.
AU - Iyengar, Sudha K.
AU - Engelman, Corinne D.
AU - Karki, Chitra K.
AU - Liu, Zhe
AU - Igo, Robert P.
AU - Truitt, Barbara
AU - Klein, Michael L.
AU - Snodderly, D. Max
AU - Blodi, Barbara A.
AU - Gehrs, Karen M.
AU - Sarto, Gloria E.
AU - Wallace, Robert B.
AU - Robinson, Jennifer
AU - LeBlanc, Erin S.
AU - Hageman, Gregory
AU - Tinker, Lesley
AU - Mares, Julie A.
PY - 2013
Y1 - 2013
N2 - PURPOSE. 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 (bA=0.029, P=2.2 3 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 3 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.
AB - PURPOSE. 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 (bA=0.029, P=2.2 3 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 3 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.
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U2 - 10.1167/iovs.12-10867
DO - 10.1167/iovs.12-10867
M3 - Article
C2 - 23404124
AN - SCOPUS:84875636747
SN - 0146-0404
VL - 54
SP - 2333
EP - 2345
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 3
ER -