Sleep Disordered Breathing, APOE and Lipid Metabolism

描述(由申请人提供)： 最近的发现表明阻塞性睡眠呼吸暂停、脂代谢和神经退行性变之间存在相互关系。载脂蛋白E epsilon 4(ApoE E4)是一种与心血管疾病(CVD)风险增加和阿尔茨海默病(AD)相关的遗传标记，与睡眠呼吸紊乱(SDB)风险增加两倍和呼吸暂停症状严重程度增加相关。初步数据显示，这种关联性在50岁至65岁之间更为明显。其他实验表明，阻塞性睡眠呼吸暂停(OSA)患者的瘦素水平失调。综上所述，这些发现提示了与阻塞性睡眠呼吸暂停综合征脂代谢失调有关的共同病理生理机制。了解这些机制对于SDB的预防和治疗至关重要。在这个项目中，我们将：1)使用病例/对照和家系设计扩大我们的发现，即APOE e4增加了普通人群中睡眠呼吸暂停的风险；2)检查其他调节血脂水平的基因的多态性是否与睡眠呼吸暂停相关；3)研究脂调节基因多态性、血脂谱(低密度脂蛋白-胆固醇、高密度脂蛋白-胆固醇、甘油三酯)、血浆瘦素(和其他脂调节激素)和睡眠呼吸暂停水平之间的关系。 这些研究将对扩大我们对睡眠呼吸暂停和代谢综合征之间的联系的理解至关重要。这项应用将集中在这个复杂的方程式中的一个方面，即脂代谢和SDB之间的关系。由于脂代谢对心血管风险至关重要，这一应用还将引发进一步的研究，重点放在充分控制SDB对心血管的影响上。

DESCRIPTION (provided by applicant): 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.