Attenuation of Genetic Risk for Age-Related Macular Degeneration by Healthy Diets and Lifestyles

Abstract

Purpose: To investigate whether the risk of age-related macular degeneration (AMD) associated with Y402H in the complement factor H (CFH) gene is modified by dietary lutein and zeaxanthin (dietary LZ) or Healthy Lifestyle Score in the Carotenoids in Age-Related Eye Disease Study (CAREDS), an ancillary study to the Women’s Health Initiative (WHI) Observational Study.

Methods: Dietary LZ for CAREDS participants was estimated using food frequency questionnaires at WHI baseline (1994-1998). Healthy Lifestyle Scores (0-6 points) were assigned based on levels of three lifestyle variables: Healthy Eating Index score, physical activity (MetHrs/week), and pack years of smoking at WHI baseline. Six years later, stereoscopic fundus photographs were taken and graded for AMD. The current analysis was restricted to 728 women, 120 with early or late AMD, for whom there was no evidence of recent diet change, history of cardiovascular disease, hypertension, diabetes, or AMD prior to assessment of diet and physical activity. Interactions between Y402H genotypes and dietary LZ or Healthy Lifestyle Score were assessed separately using a multiplicative interaction term in logistic regression models adjusted for age. The referent group was low genetic risk (TT) and low diet scores (first quintile of dietary LZ or Healthy Lifestyle Scores 0-2).

Results: Overall, the largest reduction in odds for AMD from healthy diets and lifestyles was among women homozygous for the risk allele of CFH Y402H, CC (Pinteraction=0.15). Homozygotes for the risk allele had over 2-fold lower odds of AMD when in the highest quintile of dietary LZ (OR=0.93, 95% CI: 0.21-4.17) versus the lowest quintile (OR=2.23, 95% CI: 0.56-8.91); Ptrend=0.06. The same patterns were observed for Healthy Lifestyle Score: homozygotes having a combination of unhealthy behaviors (0-2 points) vs. healthy behaviors (4-6 points) including healthy diets, physical activity and <7 packyears of smoking reduced odds for AMD from 3.21 (95% CI: 1.14-8.98) to 0.98 (95% CI: 0.37-2.60); Ptrend=0.03. Synergy between genotype and healthy lifestyle score was observed (synergy index=1.29, 95% CI: 1.12-1.49). Adjustment for hormone therapy, sunlight exposure, and iris color did not alter the conclusion.

Conclusions: These results suggest the greatest benefit of healthy diets and lifestyle in reducing odds of AMD is in women with high risk genotypes, characterized by Y402H.

Keywords: 412 age-related macular degeneration • 539 genetics • 444 carotenoids/carotenoid binding proteins