title: Smoking, dietary betaine, methionine, and vitamin D in monozygotic twins with discordant macular degeneration: epigenetic implications.
abstract: OBJECTIVE
  We evaluated monozygotic twin pairs with discordant age-related macular degeneration (AMD) phenotypes to assess differences in behavioral and nutritional factors.
  
  
  METHODS
  Case series.
  
  
  METHODS
  Caucasian male twin pairs from the United States Twin Study of Macular Degeneration.
  
  
  METHODS
  Twin pairs were genotyped to confirm monozygosity. Ocular characteristics were evaluated based on fundus photographs using the Wisconsin Grading System and a 5-grade Clinical Age-Related Maculopathy Staging System. We selected twin pairs discordant in each of the following phenotypic categories: Stage of AMD (n = 28), drusen area (n = 60), drusen size (n = 40), and increased pigment area (n = 56). The Wilcoxon signed-rank test and linear regression were used to assess associations between behavioral and nutritional characteristics and each phenotype within discordant twin pairs.
  
  
  METHODS
  Differences in smoking and dietary factors within twin pairs discordant for stage of AMD, drusen area, drusen size, and pigment area.
  
  
  RESULTS
  Representative fundus photographs depict the discordant phenotypes. Pack-years of smoking were higher for the twin with the more advanced stage of AMD (P = 0.05). Higher dietary intake of vitamin D was present in the twins with less severe AMD (P = 0.01) and smaller drusen size (P = 0.05) compared with co-twins, adjusted for smoking and age. Dietary intakes of betaine and methionine were significantly higher in the twin with lower stage of AMD (P = 0.009) and smaller drusen area (P = 0.03), respectively.
  
  
  CONCLUSIONS
  The twin with the more advanced stage of AMD, larger drusen area, drusen size, and pigment area tended to be the heavier smoker. The twin with the earlier stage of AMD, smaller drusen size and area, and less pigment tended to have higher dietary vitamin D, betaine, or methionine intake. Results suggest that behavioral and nutritional factors associated with epigenetic mechanisms are involved in the etiology of AMD, in addition to genetic susceptibility.
authors.affiliation: New England Eye Center, Tufts Medical Center, Boston, MA, USA. jseddon@tuftsmedicalcenter.org
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Seddon
authors.forename: Robyn
authors.initials: R
authors.lastname: Reynolds
authors.forename: Heeral R
authors.initials: HR
authors.lastname: Shah
authors.forename: Bernard
authors.initials: B
authors.lastname: Rosner
mesh_terms: D001519:Behavior; D001622:Betaine / Q000008:administration & dosage*; D004032:Diet; D018450:Disease Progression; D057890:Epigenomics; D006801:Humans; D008268:Macular Degeneration / Q000150:complications / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology; D008297:Male; D008715:Methionine / Q000008:administration & dosage*; D009747:Nutritional Physiological Phenomena; D010641:Phenotype; D015593:Retinal Drusen / Q000209:etiology; D012720:Severity of Illness Index; D012907:Smoking; D014430:Twins, Monozygotic; D014807:Vitamin D / Q000008:administration & dosage*
chemical_list: D014807:Vitamin D; D001622:Betaine; D008715:Methionine