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J. J. Wang, P. Mitchell, E. Rochtchina, W. Smith, R. Klein, B. E. K. Klein, T. Joshi, T. A. Sivakumaran, S. K. Iyengar, Blue Mountains Eye Study; Complement Factor H, Smoking, Dietary Fish Consumption and Age-Related Macular Degeneration: Population-Based Findings. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2882.
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To assess joint/ modifying effects of smoking and dietary fish consumption with complement factor H (CFH) genotypes on the risk of age-related macular degeneration (AMD) in an older population.
Of 3654 Blue Mountains Eye Study baseline participants aged 49+ years (1992-4), 2335 (75% of survivors) were re-examined after 5 and 1935 (75% of survivors) after 10 years. AMD incidence was confirmed via side-by-side photographic grading. Of 2452 participants who were followed, 1881 with DNA available were genotyped for the CFH 1061170 locus using Taqman assays. An additive model for CFH risk stratification was used. Among participants of first-degree family members, only the youngest member of each family was included (90 excluded). Dietary data were collected using a validated food frequency questionnaire. Fish consumption was estimated using the Australian Tables of Food Composition.
The CFH CC genotype was found in 13.6% of the population, the CT genotype in 46.7% and TT genotype in 39.7%. After adjusting for age, sex and smoking, a gradient pattern of increasing AMD risk associated with the CC and CT genotypes was evident (for Early AMD, relative risk, RR 1.8, [95% confidence interval, CI 1.2-2.8] for CT and RR 2.7 [CI 1.6-4.5] for CC; for Late AMD, RR 2.7 [CI 1.2-6.4] for CT and RR 4.8 [CI 1.8-12.7] for CC, compared to the TT genotype). There was no significant interaction (p=0.96), but a joint effect of the CFH risk allele with smoking on Late AMD risk (for non-smokers: RR 1.7 [CI 0.6-4.6] for CT and RR 4.2 [CI 1.4-12.6] for CC; for smokers: RR 10.9 [CI 3.1-38.1] for CT and RR 9.7 [CI 1.7-54.8] for CC). There was a significant interaction between the risk allele and fish consumption on Late AMD risk (p=0.03). After adjusting for age, sex, smoking, white blood cell count, weekly fish consumption was associated with a reduced risk of Late AMD in persons with the CC (RR 0.15, CI 0.03-0.8), but not with the CT (RR 0.74, CI 0.3-2.0) or TT genotype (RR 1.3, CI 0.2-7.1).
Our findings confirm the joint effects of the CFH risk allele with smoking on Late AMD risk, and show that fish consumption appears to protect against Late AMD in those with the CFH risk allele.
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