Sleep Disordered Breathing, APOE, and Lipid Metabolism

BACKGROUND:

Recent findings suggest interrelationships between obstructive sleep apnea, lipid metabolism, and neurodegeneration. Apolipoprotein E epsilon4 (APOE e4), a genetic marker linked to increased cardiovascular disease (CVD) risk and Alzheimer's disease (AD), is associated with a two fold increased risk of sleep disordered breathing (SDB), and an increase in severity of apnea symptoms. Preliminary data suggest that this association is stronger between the ages of 50 and 65. Other experiments suggest dysregulated leptin levels in obstructive sleep apnea (OSA). Taken together, these findings suggest common pathophysiological mechanisms involving dysregulated lipid metabolism in OSA. An understanding of these mechanisms is essential for the prevention and treatment of SDB.

DESIGN NARRATIVE:

Using case/control and family designs, the study: 1) extends the finding that apolipoprotein E epsilon4 (APOE e4) increases the risk of sleep apnea in the general population; 2) examines if polymorphisms in other genes regulating lipid levels are associated with sleep apnea; 3) studies the relationship between lipid regulatory gene polymorphisms, lipid profile (LDL- cholesterol, HDL-cholesterol, triglycerides), plasma leptin (and other lipid regulatory hormones), and sleep apnea levels.

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