APOE epsilon4 is associated with obstructive sleep apnea/hypopnea: the Sleep Heart Health Study.
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 epsilon4 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 epsilon4 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 > or = 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 epsilon4 allele was present in 25% of subjects, with 1.3% epsilon4/epsilon4 homozygotes. The prevalence of OSAH was 19%. After adjustment for age, sex, and BMI, the presence of any APOE epsilon4 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 > or =75 years old (OR 1.32, CI 0.91 to 1.90). Exploratory analyses revealed that the strongest effect of APOE epsilon4 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.


CONCLUSIONS
The APOE epsilon4 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.
The Pulmonary Center, Boston University School of Medicine and VA Boston Healthcare System, MA 02118-2394, USA. dgottlieb@lung.bumc.bu.edu
D J
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Gottlieb
A L
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DeStefano
D J
DJ
Foley
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Mignot
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Redline
R J
RJ
Givelber
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Young
D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000453:epidemiology; D015331:Cohort Studies; D015897:Comorbidity; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006949:Hyperlipidemias / Q000453:epidemiology; D006973:Hypertension / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology; D017286:Polysomnography; D020181:Sleep Apnea, Obstructive / Q000453:epidemiology / Q000235:genetics*; D012907:Smoking / Q000453:epidemiology
D053327:Apolipoprotein E4; D001057:Apolipoproteins E