title: Reducing the genetic risk of age-related macular degeneration with dietary antioxidants, zinc, and ω-3 fatty acids: the Rotterdam study.
abstract: OBJECTIVE
  To investigate whether dietary nutrients can reduce the genetic risk of early age-related macular degeneration (AMD) conferred by the genetic variants CFH Y402H and LOC387715 A69S in a nested case-control study.
  
  
  METHODS
  For 2167 individuals (≥55 years) from the population-based Rotterdam Study at risk of AMD, dietary intake was assessed at baseline using a semiquantitative food frequency questionnaire and genetic variants were determined using TaqMan assay. Incident early AMD was determined on fundus photographs at 3 follow-up visits (median follow-up, 8.6 years). The synergy index was used to evaluate biological interaction between risk factors; hazard ratios were calculated to estimate risk of early AMD in strata of nutrient intake and genotypes.
  
  
  RESULTS
  Five hundred seventeen participants developed early AMD. Significant synergy indices supported the possibility of biological interaction between CFH Y402H and zinc, β-carotene, lutein/zeaxanthin, and eicosapentaenoic/docosahexaenoic acid (EPA/DHA) and between LOC387715 A69S and zinc and EPA/DHA (all P < .05). Homozygotes of CFH Y402H with dietary intake of zinc in the highest tertile reduced their hazard ratio of early AMD from 2.25 to 1.27. For intakes of β-carotene, lutein/zeaxanthin, and EPA/DHA, these risk reductions were from 2.54 to 1.47, 2.63 to 1.72, and 1.97 to 1.30, respectively. Carriers of LOC387715 A69S with the highest intake of zinc and EPA/DHA reduced their risk from 1.70 to 1.17 and 1.59 to 0.95, respectively (all P trends <.05).
  
  
  CONCLUSIONS
  High dietary intake of nutrients with antioxidant properties reduces the risk of early AMD in those at high genetic risk. Therefore, clinicians should provide dietary advice to young susceptible individuals to postpone or prevent the vision-disabling consequences of AMD.
authors.affiliation: Department of Ophthalmology, Erasmus Medical Center Rotterdam, 3000 CA Rotterdam, the Netherlands.
authors.forename: Lintje
authors.initials: L
authors.lastname: Ho
authors.forename: Redmer
authors.initials: R
authors.lastname: van Leeuwen
authors.forename: Jacqueline C M
authors.initials: JC
authors.lastname: Witteman
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Paulus T V M
authors.initials: PT
authors.lastname: de Jong
authors.forename: Johannes R
authors.initials: JR
authors.lastname: Vingerling
authors.forename: Caroline C W
authors.initials: CC
authors.lastname: Klaver
mesh_terms: D000368:Aged; D000975:Antioxidants / Q000008:administration & dosage*; D001766:Blindness / Q000209:etiology / Q000517:prevention & control*; D019587:Dietary Supplements; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D008268:Macular Degeneration / Q000178:diet therapy* / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D011446:Prospective Studies; D012307:Risk Factors; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D014792:Visual Acuity; D015032:Zinc / Q000008:administration & dosage*
chemical_list: D000975:Antioxidants; D015525:Fatty Acids, Omega-3; D015032:Zinc