Objective: To examine the association between the apolipo-protein E (APOE) gene and early age-related maculopathy (ARM) in middle-aged persons. Design: Population-based cross-sectional study. Participants: Participants from the Atherosclerosis Risk in Communities Study (n=10 139; age range,49-73 years). Methods: Retinal photographywas performed on 1 randomly selected eye,and grading for presence of ARMwas carried out using a modification of the Wisconsin ARM Grading System. Early ARM was defined as the presence of either soft drusen alone,retinal pigment epithelial depigmentation alone,or a combination of soft drusen with increased retinal pigment and/or depigmentation. DNA extracted from blood samples of participants were analyzed for common allelic variants of the APOE gene ( 2, 3,and  4). Main Outcome Measures: Presence of early ARM on retinal photographs. Results: The prevalence of early ARM was similar in participants with differentAPOE genotypes:  2/ 2 (5.9% ), 2/ 3 (5.2% ), 2/ 4 (3.2% ), 3/ 3 (5.2% ), 3/ 4 (4.9% ),and  4/ 4 (4.1% ). After controlling for age,gender,race,cigarette smoking,and other factors,early ARM was not associated with APOE genotypes,with an odds ratio (OR) of 1.35 (95% confidence interval CI,0.54-3.38) for  2/ 2 genotype,an OR of 1.06 (95% CI,0.80-1.40) for  2/ 3 genotype,an OR of 0.63 (95% CI,0.32-1.24) for  2/ 4 genotype,an OR of 0.99 (95% CI,0.80-1.24) for  3/ 4 genotype,and an OR of 0.88 (95% CI,0.47-1.63) for  4/ 4 genotype,as compared with 3/3 genotype (reference). No associations were found for specific early ARM signs or in analyses stratified by age,gender,race,or cigarette smoking status. Conclusions: These data provide no evidence of a strong association between the APOE gene and early ARM in middle-aged persons. This suggests that APOE is not likely a major determinant of the early stages of ARM in younger people. However,our study does not exclude the possibility of a weaker association or that APOE may influence only the development of late ARM in older populations,as reported in other studies. Objective: To examine the association between the apolipo-protein E (APOE) gene and early age-related maculopathy (ARM) in middle-aged persons. Design: Population-based cross-sectional study. Participants: Participants from the Atherosclerosis Risk in Communities Methods: Retinal photography was performed on 1 randomly selected eye, and grading for presence of ARM was carried out using a modification of the Wisconsin ARM Grading System. Early ARM was defined as the presence of either soft drusen alone, retinal pigment epithelial depigmentation alone, or a combination of soft drusen with increased retinal pigment and / or depigmentation. DNA extracted from blood samples of participants were analyzed for common allelic variants of the APOE gene ( 2, Out 3, and  4). Main Outcome Measures: Presence of early ARM on retinal photographs. Results: The prevalence of early ARM was similar in participants with different APPO genotypes:  2 /  2 (5.9%),  2 /  3 (5.2%),  2 /  4 (3.2%),  3 /  3 (5.2%),  3 /  4 (4.9%), and  4 /  4 (4.1%). After controlling for age, gender, race, cigarette smoking, and other factors, early ARM was not associated with APOE genotypes, with an odds ratio (OR) of 1.35 (95% confidence interval CI, 0.54-3.38) for  2 /  2 genotype, an OR of 1.06 (95% CI, 0.80-1.40) for  2 /  3 genotype, an OR of 0.63 (95% CI, 0.32-1.24) for  2 /  4 genotype, an OR of 0.99 95% CI, 0.80-1.24) for  3 /  4 genotype, and an OR of 0.88 (95% CI, 0.47-1.63) for  4 /  4 genotype, as compared with 3/3 genotype associations were found for specific early ARM signs or in analyzes stratified by age, gender, race, or cigarette smoking status. Conclusions: These data provide no evidence of a strong association between the APOE gene and early ARM in middle-aged persons. that APOE is not likely a major determinant of the early stages of ARM in younger people. However, our study does not exclude the possibility of a weaker association or that APOE may influence only the development of late ARM in older populations, as reported in other studies.