Candidate gene study of macular response to supplemental lutein and zeaxanthin

Exp Eye Res. 2013 Oct;115:172-7. doi: 10.1016/j.exer.2013.07.020. Epub 2013 Jul 25.


Supplementation with carotenoids is proposed to protect against age-related macular degeneration. There is, however, considerable variability in retinal macular pigment response, which may be due to underlying genetic variation. The purpose of this study was to determine whether genetic factors, which have been previously associated with cross-sectional macular pigment levels in the retina or serum lutein, also influence response to supplementation. To this end we conducted an association study in 310 subjects from the TwinsUK cohort between variants in 8 candidate genes and serum lutein and retinal macular pigment optical density (MPOD) levels before and after supplementation. Four variants were associated with MPOD response to supplementation (p < 0.05): rs11057841 (SCARB1), rs4926339 (RPE65), rs1929841 (ABCA1) and rs174534 (FADS1). We also confirmed previous associations between rs6564851 near BMCO1 (p < 0.001) and rs11057841 within SCARB1 (p = 0.01) and baseline measures of serum lutein; while the latter was also associated with MPOD response, none of the BMCO1 variants were. Finally, there was evidence for association between variants near RPE65 and ELOVL2 and changes in lutein concentration after supplementation. This study is the first to show association between genetic variants and response to carotenoids supplementation. Our findings suggest an important link between MP response and the biological processes of carotenoids transport and fatty acid metabolism.

Keywords: CAREDS; Carotenoids in Age Related Eye Disease Study; L; LZ; MP; MPOD; Z; genetics; lutein; lutein and zeaxanthin; macular degeneration; macular pigment; macular pigment optical density; supplementation; zeaxanthin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Twin Study

MeSH terms

  • ATP Binding Cassette Transporter 1 / genetics
  • Adult
  • Chromatography, High Pressure Liquid
  • Delta-5 Fatty Acid Desaturase
  • Dietary Supplements
  • Fatty Acid Desaturases / genetics
  • Female
  • Genetic Variation
  • Genotype
  • Humans
  • Lutein / administration & dosage*
  • Lutein / blood
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • Quantitative Trait, Heritable*
  • Retinal Pigments / genetics*
  • Retinal Pigments / metabolism
  • Scavenger Receptors, Class B / genetics
  • Twins, Dizygotic / genetics*
  • Twins, Monozygotic / genetics*
  • Xanthophylls / administration & dosage*
  • Xanthophylls / blood
  • Young Adult
  • Zeaxanthins
  • cis-trans-Isomerases / genetics


  • ABCA1 protein, human
  • ATP Binding Cassette Transporter 1
  • Delta-5 Fatty Acid Desaturase
  • Retinal Pigments
  • SCARB1 protein, human
  • Scavenger Receptors, Class B
  • Xanthophylls
  • Zeaxanthins
  • Fatty Acid Desaturases
  • FADS1 protein, human
  • retinoid isomerohydrolase
  • cis-trans-Isomerases
  • Lutein