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Unlabelled: The epsilon4 allele of apolipoprotein E (APOE) has been associated with health-related outcomes that may adversely affect quality of life (QOL) in older adults. In the absence of published information, we sought to determine whether the epsilon4 allele was associated with subjective QOL across 5 parameters in a community sample of older adults., Design: Prospective cohort study., Setting: Community-based sample of older adults in North Carolina (Duke site of the Established Populations for Epidemiologic Studies of the Elderly [Duke EPESE])., Participants: Self-responding genotyped sample members (n = 1,880) of whom 1,254 provided longitudinal data., Measurements: APOE genotype and five newly constructed, reliable, and valid measures of subjective QOL derived from the Duke EPESE questionnaire. The 5 parameters measured were social, economic, mental and physical health, and functional status. Control variables included age, gender, race (African American or White), education and urban/rural residence., Results: Among those with good baseline QOL, there was no significant association between the epsilon4 allele and any of the parameters of subjective QOL in longitudinal analyses. In controlled longitudinal analysis, older age women predicted poorer functional status; being African American, and reporting lower education predicted poorer subjective economic well-being; and being African American predicted better self-assessed mental health., Conclusions: This study is among the first to explore the association of the epsilon4 allele with overall QOL. Considered from a public health perspective, these findings challenge the uncritical assumption that the presence of this susceptibility gene in the population implies an excess burden of poor QOL. The findings do not contradict the previous association of epsilon4 with Alzheimer's disease (AD) and other conditions. Such conditions continue to merit full attention.