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APOE epsilon4 is associated with obstructive sleep apnea/hypopnea: the Sleep Heart Health Study.

TitleAPOE epsilon4 is associated with obstructive sleep apnea/hypopnea: the Sleep Heart Health Study.
Publication TypeJournal Article
Year of Publication2004
AuthorsGottlieb, DJ, DeStefano, AL, Foley, DJ, Mignot, E, Redline, S, Givelber, RJ, Young, T
JournalNeurology
Volume63
Issue4
Pagination664-8
Date Published2004 Aug 24
ISSN1526-632X
KeywordsAdult, Age Distribution, Aged, Aged, 80 and over, Alleles, Apolipoprotein E4, Apolipoproteins E, Cardiovascular Diseases, Cohort Studies, Comorbidity, Female, Genetic Predisposition to Disease, Genotype, Humans, Hyperlipidemias, Hypertension, Male, Middle Aged, Obesity, Polysomnography, Sleep Apnea, Obstructive, Smoking
Abstract<p><b>BACKGROUND: </b>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.</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSION: </b>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.</p>
DOI10.1212/01.wnl.0000134671.99649.32
Alternate JournalNeurology
PubMed ID15326239
Grant ListR01 HL71515 / HL / NHLBI NIH HHS / United States
U01 HL53916 / HL / NHLBI NIH HHS / United States
U01 HL53931 / HL / NHLBI NIH HHS / United States
U01 HL53934 / HL / NHLBI NIH HHS / United States
U01 HL53937 / HL / NHLBI NIH HHS / United States
U01 HL53938 / HL / NHLBI NIH HHS / United States
U01 HL53940 / HL / NHLBI NIH HHS / United States
U01 HL53941 / HL / NHLBI NIH HHS / United States
U01 HL63429 / HL / NHLBI NIH HHS / United States
U01 HL63463 / HL / NHLBI NIH HHS / United States
U01 HL64360 / HL / NHLBI NIH HHS / United States