CONTEXT: Studies have reported that single-nucleotide polymorphisms in the genes CFH and LOC387715 are associated with age-related macular degeneration (AMD). OBJECTIVE: To assess whether these genetic variants have prognostic importance for progression to advanced AMD and related visual loss. DESIGN, SETTING, AND PARTICIPANTS: Prospective analysis of 1466 white participants in the Age-Related Eye Disease Study (AREDS), a US multicenter clinical trial conducted from 1990 to 2001 with a mean follow-up time of 6.3 years. Age-related macular degeneration status was determined by grading of fundus photographs. Progression (n = 281) was defined as newly diagnosed advanced AMD (geographic atrophy, exudative disease, or AMD causing visual loss) in one or both eyes during the course of the study. Genotypic analysis was conducted in 2006. MAIN OUTCOME MEASURE: Incidence rates of dry and neovascular advanced AMD. RESULTS: The CFH Y402H and LOC387115 A69S polymorphisms were each independently related to progression from early or intermediate stages to advanced stages of AMD, controlling for demographic factors, smoking, body mass index, and AREDS vitamin-mineral treatment assignment, with odds ratios (ORs) of 2.6 (95% confidence interval [CI], 1.7-3.9) for CFH and 4.1 (95% CI, 2.7-6.3) for LOC387715 for the homozygous risk genotypes (P<.001 for trend for each additional risk allele for both genes). The effect of LOC387715 was stronger for progression to neovascular disease (OR, 6.1; 95% CI, 3.3-11.2) compared with geographic atrophy (OR, 3.0; 95% CI, 1.4-6.5) relative to no progression for the homozygous risk state. The presence of all adverse factors (both risk genotypes, smoking, and body mass index > or =25) increased risk 19-fold. Smoking and high body mass index increased odds of progression within each risk genotype. Genetic plus nongenetic risk scores provided an area under the receiver operating characteristic curve of up to 0.78. CONCLUSIONS: Common polymorphisms in the genes CFH and LOC387715 are independently related to AMD progression after adjustment for other known AMD risk factors. Presence of these polymorphisms plus smoking [corrected] and body mass index of 25 or higher, controlling for AREDS vitamin-mineral treatment, identifies [corrected] patients who are highly susceptible to developing advanced states [corrected] of this visually disabling disease.
CONTEXT: Studies have reported that single-nucleotide polymorphisms in the genes CFH and LOC387715 are associated with age-related macular degeneration (AMD). OBJECTIVE: To assess whether these genetic variants have prognostic importance for progression to advanced AMD and related visual loss. DESIGN, SETTING, AND PARTICIPANTS: Prospective analysis of 1466 white participants in the Age-Related Eye Disease Study (AREDS), a US multicenter clinical trial conducted from 1990 to 2001 with a mean follow-up time of 6.3 years. Age-related macular degeneration status was determined by grading of fundus photographs. Progression (n = 281) was defined as newly diagnosed advanced AMD (geographic atrophy, exudative disease, or AMD causing visual loss) in one or both eyes during the course of the study. Genotypic analysis was conducted in 2006. MAIN OUTCOME MEASURE: Incidence rates of dry and neovascular advanced AMD. RESULTS: The CFHY402H and LOC387115 A69S polymorphisms were each independently related to progression from early or intermediate stages to advanced stages of AMD, controlling for demographic factors, smoking, body mass index, and AREDS vitamin-mineral treatment assignment, with odds ratios (ORs) of 2.6 (95% confidence interval [CI], 1.7-3.9) for CFH and 4.1 (95% CI, 2.7-6.3) for LOC387715 for the homozygous risk genotypes (P<.001 for trend for each additional risk allele for both genes). The effect of LOC387715 was stronger for progression to neovascular disease (OR, 6.1; 95% CI, 3.3-11.2) compared with geographic atrophy (OR, 3.0; 95% CI, 1.4-6.5) relative to no progression for the homozygous risk state. The presence of all adverse factors (both risk genotypes, smoking, and body mass index > or =25) increased risk 19-fold. Smoking and high body mass index increased odds of progression within each risk genotype. Genetic plus nongenetic risk scores provided an area under the receiver operating characteristic curve of up to 0.78. CONCLUSIONS: Common polymorphisms in the genes CFH and LOC387715 are independently related to AMD progression after adjustment for other known AMD risk factors. Presence of these polymorphisms plus smoking [corrected] and body mass index of 25 or higher, controlling for AREDS vitamin-mineral treatment, identifies [corrected] patients who are highly susceptible to developing advanced states [corrected] of this visually disabling disease.
Authors: Elizabeth Monaghan-Benson; John Hartmann; Aleksandr E Vendrov; Steve Budd; Grace Byfield; Augustus Parker; Faisal Ahmad; Wei Huang; Marschall Runge; Keith Burridge; Nageswara Madamanchi; M Elizabeth Hartnett Journal: Am J Pathol Date: 2010-08-27 Impact factor: 4.307
Authors: Zohar Yehoshua; Philip J Rosenfeld; Giovanni Gregori; William J Feuer; Manuel Falcão; Brandon J Lujan; Carmen Puliafito Journal: Ophthalmology Date: 2010-10-29 Impact factor: 12.079
Authors: Jie Jin Wang; Elena Rochtchina; Wayne Smith; Ronald Klein; Barbara E K Klein; Tripti Joshi; Theru A Sivakumaran; Sudha Iyengar; Paul Mitchell Journal: Am J Epidemiol Date: 2008-12-13 Impact factor: 4.897
Authors: Haibo Wang; Yanchao Jiang; Dallas Shi; Lawrence A Quilliam; Magdalena Chrzanowska-Wodnicka; Erika S Wittchen; Dean Y Li; M Elizabeth Hartnett Journal: FASEB J Date: 2013-09-16 Impact factor: 5.191
Authors: Ronald E Gangnon; Kristine E Lee; Barbara E K Klein; Sudha K Iyengar; Theru A Sivakumaran; Ronald Klein Journal: Invest Ophthalmol Vis Sci Date: 2014-03-20 Impact factor: 4.799