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. In this project, we will: 1) extend our finding that APOE e4 increases the risk of sleep apnea in the general population using case/control and family designs; 2) examine if polymorphisms in other genes regulating lipid levels are associated with sleep apnea; 3) study 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. These studies will be critical to extend our understanding of the association between sleep apnea and the metabolic syndrome. This application will focus on one arm of this complex equation, the relationship between lipid metabolism and SDB. With lipid metabolism being critical to cardiovascular risk, this application will also trigger further studies focusing on cardiovascular impact with adequate control of SDB.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL071515-04
Application #
6952694
Study Section
Special Emphasis Panel (ZHL1-CSR-P (S1))
Program Officer
Twery, Michael
Project Start
2002-09-21
Project End
2008-07-31
Budget Start
2005-08-01
Budget End
2008-07-31
Support Year
4
Fiscal Year
2005
Total Cost
$359,279
Indirect Cost
Name
Stanford University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Winkelman, John W; Redline, Susan; Baldwin, Carol M et al. (2009) Polysomnographic and health-related quality of life correlates of restless legs syndrome in the Sleep Heart Health Study. Sleep 32:772-8
Winkelman, John W; Shahar, Eyal; Sharief, Imran et al. (2008) Association of restless legs syndrome and cardiovascular disease in the Sleep Heart Health Study. Neurology 70:35-42
Patel, Sanjay R; Larkin, Emma K; Mignot, Emmanuel et al. (2007) The association of angiotensin converting enzyme (ACE) polymorphisms with sleep apnea and hypertension. Sleep 30:531-3
Taheri, Shahrad; Austin, Diane; Lin, Ling et al. (2007) Correlates of serum C-reactive protein (CRP)--no association with sleep duration or sleep disordered breathing. Sleep 30:991-6
Larkin, Emma K; Patel, Sanjay R; Redline, Susan et al. (2006) Apolipoprotein E and obstructive sleep apnea: evaluating whether a candidate gene explains a linkage peak. Genet Epidemiol 30:101-10
Guilleminault, Christian; Kirisoglu, Ceyda; Ohayon, Maurice M (2004) C-reactive protein and sleep-disordered breathing. Sleep 27:1507-11
Gottlieb, D J; DeStefano, A L; Foley, D J et al. (2004) APOE epsilon4 is associated with obstructive sleep apnea/hypopnea: the Sleep Heart Health Study. Neurology 63:664-8
Lin, Ling; Finn, Laurel; Zhang, Jing et al. (2004) Angiotensin-converting enzyme, sleep-disordered breathing, and hypertension. Am J Respir Crit Care Med 170:1349-53
Taheri, Shahrad; Lin, Ling; Austin, Diane et al. (2004) Short sleep duration is associated with reduced leptin, elevated ghrelin, and increased body mass index. PLoS Med 1:e62