Combined Effects of Complement Factor H Genotypes, Fish Consumption, and Inflammatory Markers on Long-Term Risk for Age-related Macular Degeneration in a Cohort

Abstract

At baseline in 1992-1994, the authors assessed the combined effects of complement factor H (CFH) genotypes with smoking, fish consumption, and inflammatory markers on the risk of age-related macular degeneration (AMD) in 3,654 persons aged > or =49 years. They reexamined 75% of the survivors after 5 and 10 years, confirming incident AMD by side-by-side photographic grading. Of the 2,452 persons followed in the Blue Mountains Eye Study, 1,881 were genotyped (rs1061170), with CC, CT, and TT identified in 13.6%, 46.7%, and 39.7%, respectively. AMD risk increased with each additional C allele (early AMD: age- and sex-adjusted relative risk (RR) = 1.6, 95% confidence interval (CI): 1.2, 1.9; late AMD: RR = 2.3, 95% CI: 1.5, 3.6). Late AMD risk among current smokers with the CC/CT genotypes (RR = 10.7, 95% CI: 3.4, 33.9) was 5-fold that for genotypically similar nonsmokers (RR = 2.2, 95% CI: 0.9, 5.5) versus current nonsmokers with TT genotypes. Weekly compared with less than weekly consumption of fish was associated with reduced late AMD risk in participants with the CC genotype (RR = 0.15, 95% CI: 0.03, 0.8) but not the CT (RR = 0.7, 95% CI: 0.3, 2.0) or TT (RR = 1.3, 95% CI: 0.2, 7.2) genotypes. This study documents joint contributions from genetic and systemic factors in determining the progression of AMD.

Reducing the Genetic Risk of Age-Related Macular Degeneration With Dietary Antioxidants, Zinc, and ω-3 Fatty Acids

“…Thus, whether the protection offered by these nutrients is sufficient to counteract the genetic risk is unclear. 32,33 Within the framework of the large population-based Rotterdam Study, we explored the relationship between a healthy diet, genetic risk, and early AMD. We assessed the intake of antioxidants, zinc, and -3 fatty acids in daily foods, diagnosed the onset of early AMD during a lengthy follow-up, and investigated the risk-reducing effect of these nutrients in the various genotypes of CFH Y402H and LOC387715 A69S.…”

Nutritional Supplement Use and Age-Related Macular Degeneration

“…Many studies have provided evidence for a protective role of omega-3 fatty acids supplementation in AMD risk 91,[106][107][108][109][110][111][112][113][114][115][116][117] . The first study evaluating the relationship between dietary fat and AMD was published by Mares-Perlman et al 106 .…”

“…In the Blue Mountains Study group, 1881 participants were genotyped for complement factor H (CFH) genetic variants 117 . Wang et al reported that AMD risk increased with each additional C allele.…”

The Age-Related Eye Disease 2 Study: Micronutrients in the Treatment of Macular Degeneration

“…n-3 LC-PUFAs may increase the macular pigment density, which alters blue light penetration and has local antioxidant and anti-inflammatory activities (131). Increased fish and n-3 FA consumption has also been correlated with decreased AMD risk (50,(132)(133)(134)(135). As the primary FA in the retina, DHA helps regenerate rhodopsin, thereby reducing oxidative stress.…”