A Variant in Lipid Regulator FADS1 is Associated with the Risk of AMD in the Rotterdam Study

Abstract

Purpose : Long-chain n-3 polyunsaturated fatty acids (PUFAs) have been shown to reduce the risk of age-related macular degeneration (AMD). PUFAs can come directly from dietary intake or from conversion of a-Linolenic Acid (ALA) to eicosapentaenoic acid (EPA) and docosahexaeenzuur acid (DHA). The Fatty Acid Desaturase 1 (FADS1) gene is involved in polyunsaturated fatty acid biosynthesis and harbours variants which appear to be associated with higher ALA and lower EPA and DHA concentrations. We evaluated the relationship between a polymorphism in FADS1 and AMD, and investigated whether this relationship was influenced by dietary EPA/DHA intake.

Methods : We included 3131 individuals 55+ years from the population-based Rotterdam Study I, II and III who had dietary data obtained by 389-item food frequency questionnaire at baseline. Presence of Early and Late AMD was diagnosed on fundus photographs. Genotypes from rs174547 within FADS1 were available from GWAS imputation data. The association between the genotypes and AMD were analyzed using Logistic regression models, and subsequently stratified for three tertiles of EPA/DHA intake.

Results : A total of 658 persons developed Early AMD and 64 Late AMD. The FADS1 polymorphism rs174547 (MAF 30%) had a significantly higher risk of any AMD (odds ratio (OR) 1.14 [95% Confidence Interval (CI) 1.00-1.30] P for trend = 0.049). EPA/DHA intake appeared to influence this association. Compared to those with the lowest intake of EPA/DHA, carriers of the risk variant (T) who had higher intakes of EPA/DHA decreased their risk of AMD (OR decreased from 1.13 to 0.71; P trend = 0.029). Those who carried the non-risk allele (C) had the highest benefit from increased EPA/DHA intake (OR 0.49; P trend 0.006).

Conclusions : The FADS1 polymorphism rs174547 is associated with increased risk of AMD, but the risk can be counteracted by dietary intake of EPA/DHA. These findings suggest that dietary advice may need to be personalized towards genetic background.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.