title: CFH Y402H and ARMS2 A69S Polymorphisms and Oral Supplementation with Docosahexaenoic Acid in Neovascular Age-Related Macular Degeneration Patients: The NAT2 Study.
abstract: OBJECTIVE
  Genetic susceptibility could be modified by environmental factors and may also influence differential responses to treatments for age-related macular degeneration (AMD). We investigated whether genotype could influence response to docosahexaenoic acid (DHA)-supplementation in the occurrence of choroidal new vessels (CNV).
  
  
  METHODS
  The Nutritional AMD Treatment 2 (NAT2) study was a randomized, placebo-controlled, double-blind, parallel, comparative study, including 250 patients aged 55 to 85 years with early lesions of age-related maculopathy, visual acuity better than 0.4 Logarithm of Minimum Angle of Resolution units in the study eye and neovascular AMD in the fellow eye. Patients were randomized at baseline to receive either 3 daily fish-oil capsules, each containing 280 mg DHA, 90 mg EPA and 2 mg Vitamin E, or placebo.
  
  
  RESULTS
  Patients carrying the risk allele (C) for CFH Y402H had no statistically significant increased risk for developing CNV in the study eye (Hazard Ratio (HR)=0.97; 95% Confidence Interval (CI): 0.54-1.76 for heterozygous and HR=1.29; 95%CI: 0.69-2.40 for homozygous). Patients carrying the risk allele (T) for ARMS2 A69S had no statistically significant increased risk for developing CNV in the study eye (HR=1.68; 95%CI: 0.91-3.12) for heterozygous and HR=1.78; 95%CI: 0.90-3.52 for homozygous). A significant interaction was observed between CFH Y402H and DHA-supplementation (p=0.01). We showed a protective effect of DHA-supplementation among homozygous non-risk patients. Among these patients, occurrence of CNV was 38.2% in placebo group versus 16.7% in DHA group (p=0.008).
  
  
  CONCLUSIONS
  These results suggest that a genetic predisposition to AMD conferred by the CFH Y402H variant limits the benefit provided by DHA supplementation.
  
  
  BACKGROUND
  ISRCTN registry 98246501.
authors.affiliation: Ophthalmology Department, Hôpital Intercommunal de Créteil, University Paris Est Créteil, Créteil, France.
authors.forename: Bénédicte M J
authors.initials: BM
authors.lastname: Merle
authors.affiliation: Université de Lille Nord de France, INSERM774 Institut Pasteur de Lille, Lille, France; Université de Lille Nord de France, Lille, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Richard
authors.affiliation: CHRU de Lille, Lille, France; APHP - Saint-Antoine Hospital, Endocrinology and Metabolic Disease Department, F75012 Paris, France; Lille 2 University, School of Medicine, Department of Biochemistry and Molecular Biology, F-59045 Lille, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Benlian
authors.affiliation: Ophthalmology Department, Hôpital Intercommunal de Créteil, University Paris Est Créteil, Créteil, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Puche
authors.affiliation: INSERM, Centre INSERM U897-Epidemiologie-Biostatistique, F-33000 Bordeaux, France; Univ. Bordeaux, ISPED, F-33000 Bordeaux, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Delcourt
authors.affiliation: Ophthalmology Department, Hôpital Intercommunal de Créteil, University Paris Est Créteil, Créteil, France.
authors.forename: Eric H
authors.initials: EH
authors.lastname: Souied
mesh_terms: D000368:Aged; D017242:Complement Factor H / Q000235:genetics*; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008268:Macular Degeneration / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*
chemical_list: C514392:ARMS2 protein, human; D011506:Proteins; D004281:Docosahexaenoic Acids; D017242:Complement Factor H