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Randomized Controlled Trial
. 2015 Jul 1;10(7):e0130816.
doi: 10.1371/journal.pone.0130816. eCollection 2015.

CFH Y402H and ARMS2 A69S Polymorphisms and Oral Supplementation with Docosahexaenoic Acid in Neovascular Age-Related Macular Degeneration Patients: The NAT2 Study

Bénédicte M J Merle  1 , Florence Richard  2 , Pascale Benlian  3 , Nathalie Puche  1 , Cécile Delcourt  4 , Eric H Souied  1
Affiliations
Randomized Controlled Trial

CFH Y402H and ARMS2 A69S Polymorphisms and Oral Supplementation with Docosahexaenoic Acid in Neovascular Age-Related Macular Degeneration Patients: The NAT2 Study

Bénédicte M J Merle et al. PLoS One. .

Abstract

Purpose: 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.

Trial registration: ISRCTN registry 98246501.

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Conflict of interest statement

Competing Interests: The authors have read the journal's policy and have the following competing interests: BM received grants from Fédération des Aveugles et Handicapés Visuels de France and Fondation Nestlé France, received payment for lectures from Laboratoires Théa and Bausch & Lomb and travel accommodations from laboratoires Théa; FR none; PB received payment for lectures from Laboratoires Bausch & Lomb; NP none; CD has board membership for Laboratoires Théa and Bausch & Lomb, received consulting support from Novartis, Bayer and Allergan, and received grant from Laboratoires Théa; ES has received consulting support from Bausch & Lomb, support for travel to meeting and fees for participation in review activities from Bausch & Lomb, has board membership for Novartis, Bayer, Laboratoires Théa and Allergan, and is consultant for Novartis and Bayer. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Diagram showing the population of Nutritional AMD Treatment 2 Study design included in this paper.
Full analysis set (FAS) included patients having at least one post baseline value regarding occurrence of CNV. AMD: age-related macular degeneration; CNV: choroidal neovascularization; DHA: docosahexaenoic acid.
See this image and copyright information in PMC

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