03280nas a2200481 4500008004100000022001400041245010100055210006900156260001600225300001000241490000700251520200000258653001002258653002102268653000902289653002202298653001202320653002202332653002202354653002802376653001902404653001602423653001102439653003802450653001302488653001102501653002002512653001702532653000902549653001602558653001202574653002002586653002902606653001202635100001902647700002002666700001602686700001402702700001502716700001902731700001302750856003502763 2004 eng d a1526-632X00aAPOE epsilon4 is associated with obstructive sleep apnea/hypopnea: the Sleep Heart Health Study.0 aAPOE epsilon4 is associated with obstructive sleep apneahypopnea c2004 Aug 24 a664-80 v633 a
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.
CONCLUSION: 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.
10aAdult10aAge Distribution10aAged10aAged, 80 and over10aAlleles10aApolipoprotein E410aApolipoproteins E10aCardiovascular Diseases10aCohort Studies10aComorbidity10aFemale10aGenetic Predisposition to Disease10aGenotype10aHumans10aHyperlipidemias10aHypertension10aMale10aMiddle Aged10aObesity10aPolysomnography10aSleep Apnea, Obstructive10aSmoking1 aGottlieb, D, J1 aDeStefano, A, L1 aFoley, D, J1 aMignot, E1 aRedline, S1 aGivelber, R, J1 aYoung, T uhttps://chs-nhlbi.org/node/798