title: Candidate gene study of macular response to supplemental lutein and zeaxanthin.
abstract: 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.
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, UK.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Yonova-Doing
authors.forename: Pirro G
authors.initials: PG
authors.lastname: Hysi
authors.forename: Cristina
authors.initials: C
authors.lastname: Venturini
authors.forename: Katie M
authors.initials: KM
authors.lastname: Williams
authors.forename: Abhishek
authors.initials: A
authors.lastname: Nag
authors.forename: Stephen
authors.initials: S
authors.lastname: Beatty
authors.forename: S H Melissa
authors.initials: SH
authors.lastname: Liew
authors.forename: Clare E
authors.initials: CE
authors.lastname: Gilbert
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Hammond
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics; D000328:Adult; D002851:Chromatography, High Pressure Liquid; D000090943:Delta-5 Fatty Acid Desaturase; D019587:Dietary Supplements; D044943:Fatty Acid Desaturases / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D014975:Lutein / Q000008:administration & dosage* / Q000097:blood; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D019655:Quantitative Trait, Heritable; D012168:Retinal Pigments / Q000235:genetics* / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000235:genetics; D014429:Twins, Dizygotic / Q000235:genetics*; D014430:Twins, Monozygotic / Q000235:genetics*; D024341:Xanthophylls / Q000008:administration & dosage* / Q000097:blood; D055815:Young Adult; D065146:Zeaxanthins; D019745:cis-trans-Isomerases / Q000235:genetics; D000099178:Retinoid Isomerohydrolase
chemical_list: D064286:ATP Binding Cassette Transporter 1; D000090943:Delta-5 Fatty Acid Desaturase; D044943:Fatty Acid Desaturases; D014975:Lutein; D012168:Retinal Pigments; D051122:Scavenger Receptors, Class B; D024341:Xanthophylls; D065146:Zeaxanthins; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase; C577836:ABCA1 protein, human; C495124:SCARB1 protein, human; C000716847:FADS1 protein, human
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
references.citation: Am J Hum Genet. 2009 Feb;84(2):123-33
references.pmid: 19185284
references.citation: Nat Genet. 2013 Apr;45(4):433-9, 439e1-2
references.pmid: 23455636
references.citation: Ophthalmology. 2001 Apr;108(4):697-704
references.pmid: 11297486
references.citation: Ophthalmology. 2013 Aug;120(8):1632-40
references.pmid: 23562302
references.citation: PLoS Genet. 2009 Jan;5(1):e1000338
references.pmid: 19148276
references.citation: Cell. 2004 Jun 11;117(6):761-71
references.pmid: 15186777
references.citation: Nutr Rev. 2005 Jan;63(1):9-15
references.pmid: 15730230
references.citation: Ophthalmology. 2012 Mar;119(3):571-80
references.pmid: 22176800
references.citation: Vision Res. 1996 Jul;36(13):2001-12
references.pmid: 8759440
references.citation: Br J Ophthalmol. 2009 Aug;93(8):1116-20
references.pmid: 19304587
references.citation: Hum Mol Genet. 2012 Sep 15;21(18):4138-50
references.pmid: 22694956
references.citation: FASEB J. 2000 May;14(7):835-46
references.pmid: 10783137
references.citation: Invest Ophthalmol Vis Sci. 2011 Nov 29;52(12):9207-17
references.pmid: 21979997
references.citation: Ophthalmology. 2010 May;117(5):921-7
references.pmid: 20110127
references.citation: FEBS Lett. 2007 Jul 10;581(17):3157-63
references.pmid: 17583696
references.citation: PLoS One. 2009 Oct 05;4(10):e7341
references.pmid: 19806217
references.citation: Invest Ophthalmol Vis Sci. 2012 Mar 09;53(3):1204-10
references.pmid: 22273721
references.citation: Am J Clin Nutr. 1995 Sep;62(3):604-10
references.pmid: 7661123
references.citation: FASEB J. 2002 Aug;16(10):1289-91
references.pmid: 12154001
references.citation: Arch Ophthalmol. 2001 Oct;119(10):1455-62
references.pmid: 11594944
references.citation: Curr Opin Lipidol. 2001 Apr;12(2):129-40
references.pmid: 11264984
references.citation: Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16182-7
references.pmid: 17060630
references.citation: Invest Ophthalmol Vis Sci. 2007 Sep;48(9):4226-31
references.pmid: 17724211
references.citation: Invest Ophthalmol Vis Sci. 2006 Jun;47(6):2329-35
references.pmid: 16723441
references.citation: Invest Ophthalmol Vis Sci. 2012 Jul 26;53(8):4963-8
references.pmid: 22700713
references.citation: Prog Retin Eye Res. 2001 Mar;20(2):227-53
references.pmid: 11173253
references.citation: Exp Eye Res. 2006 May;82(5):828-39
references.pmid: 16364293
references.citation: Invest Ophthalmol Vis Sci. 2005 Dec;46(12):4430-6
references.pmid: 16303930
references.citation: Invest Ophthalmol Vis Sci. 2013 Mar 28;54(3):2333-45
references.pmid: 23404124
references.citation: PLoS Genet. 2009 Jun;5(6):e1000529
references.pmid: 19543373
references.citation: Mutat Res. 2003 Aug 5;539(1-2):117-25
references.pmid: 12948820
references.citation: Clin Exp Optom. 2002 Nov;85(6):372-7
references.pmid: 12452788
references.citation: JAMA. 2013 May 15;309(19):2005-15
references.pmid: 23644932
references.citation: Am J Clin Nutr. 2001 Dec;74(6):796-802
references.pmid: 11722962
references.citation: Genes Immun. 2010 Dec;11(8):609-21
references.pmid: 20861866
references.citation: Cancer Res. 1999 Aug 15;59(16):3985-90
references.pmid: 10463596
references.citation: Twin Res. 2001 Dec;4(6):464-77
references.pmid: 11780939
references.citation: Br J Ophthalmol. 2011 Dec;95(12):1638-45
references.pmid: 21890786
references.citation: Prog Retin Eye Res. 2004 Sep;23(5):523-31
references.pmid: 15302349
references.citation: Ophthalmology. 1999 Jun;106(6):1049-55
references.pmid: 10366070
references.citation: Surv Ophthalmol. 2000 Sep-Oct;45(2):115-34
references.pmid: 11033038
references.citation: J Biol Chem. 2000 Jan 21;275(3):2003-8
references.pmid: 10636903
references.citation: Biochim Biophys Acta. 2012 Jan;1821(1):78-87
references.pmid: 21569862
references.citation: Invest Ophthalmol Vis Sci. 2007 Aug;48(8):3783-7
references.pmid: 17652752
references.citation: Eur J Nutr. 2010 Sep;49(6):327-36
references.pmid: 20082082
references.citation: Hum Mol Genet. 2011 Sep 15;20(18):3699-709
references.pmid: 21665990
references.citation: Br J Nutr. 2008 Dec;100(6):1307-14
references.pmid: 18405400
references.citation: Arch Ophthalmol. 2000 Mar;118(3):351-8
references.pmid: 10721957