APOE ε4 is associated with obstructive sleep apnea/hypopnea
The Sleep Heart Health Study
Abstract
Background: Obstructive sleep apnea/hypopnea (OSAH) has a strong heritable component, although its genetic basis remains largely unknown. One epidemiologic study found a significant association between the APOE ε4 allele and OSAH in middle-aged adults, a finding that was not replicated in a cohort of elderly adults. The objective of this study was to further examine the association of the APOE ε4 allele with OSAH in a community-dwelling cohort, exploring age dependency of the association.
Methods: A genetic association study was performed, nested within a prospective cohort study of the cardiovascular consequences of OSAH. Unattended, in-home nocturnal polysomnography was used to measure apnea-hypopnea index (AHI) in 1,775 participants age 40 to 100 years. OSAH was defined as an AHI ≥ 15. The relation of APOE genotype to prevalent OSAH was analyzed using generalized estimating equations to account for non-independent observations of individuals from the same sibship.
Results: At least one APOE ε4 allele was present in 25% of subjects, with 1.3% ε4/ε4 homozygotes. The prevalence of OSAH was 19%. After adjustment for age, sex, and BMI, the presence of any APOE ε4 allele was associated with increased odds of OSAH (OR 1.41, 95% CI 1.06 to 1.87, p = 0.02). The effect was approximately twice as great in subjects <75 (OR 1.61, CI 1.02 to 2.54) as in those ≥75 years old (OR 1.32, CI 0.91 to 1.90). Exploratory analyses revealed that the strongest effect of APOE ε4 was in subjects age <65 (OR 3.08, CI 1.43 to 6.64), and was stronger in those with hypertension or cardiovascular disease than in those without.
Conclusion: The APOE ε4 allele is associated with increased risk of OSAH, particularly in individuals under age 65. The mechanisms underlying this association are uncertain. Age-dependency of the APOE-OSAH association may explain previous conflicting results.
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Information & Authors
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Published In
Neurology®
Volume 63 • Number 4 • August 24, 2004
Pages: 664-668
Copyright
© 2004.
Publication History
Received: November 14, 2003
Accepted: April 26, 2004
Published online: August 23, 2004
Published in print: August 24, 2004
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