Interactions among Depressive Symptoms and Genetic Influences on Cardiac Outcomes

描述（由申请人提供）：急性冠脉综合征（ACS）合并抑郁症的患者发生后续主要不良冠脉事件（MACE：心肌梗死、血运重建术、中风和死亡）的风险更高。抑郁症状与炎症蛋白水平升高有关，但仅在某些个体中存在。我们提出的是测试炎症蛋白基因多态性是否与抑郁症相互作用，导致炎症蛋白水平比基因多态性或抑郁症单独引起的炎症蛋白水平增加更大，从而增加后续MACE的风险。具体目的是确定1)抑郁是否与MACE风险相关；2) ACS期间炎症蛋白水平有无抑郁差异；3)所选择的遗传多态性是否与炎症蛋白水平有关；4)基因多态性和抑郁症状是否相互作用影响炎症蛋白水平；5)基因多态性和抑郁症状是否相互作用影响MACE的风险。炎症蛋白和基因包括：白细胞介素（IL） 6、c反应蛋白（CRP）、肿瘤坏死因子α (TNFa)、e选择素（SELE）和单核细胞趋化蛋白-1 （MCP-1）。对约1300名ACS患者，在入院后不久进行心脏介入治疗前采集一次血液样本进行基因和蛋白质工作，并在入院后2-5天内评估一次抑郁症。MACE的发生随访2年。数据将使用逻辑回归和生存分析进行分析。

DESCRIPTION (provided by applicant): Patients with acute coronary syndromes (ACS) with depression are at greater risk for subsequent major adverse coronary events (MACE: myocardial infarctions, revascularization procedures, strokes, and death). Depressive symptoms are associated with increased inflammatory protein levels, but only in certain individuals. Proposed is to test if inflammatory protein gene polymorphisms interact with depression resulting in even greater increases in inflammatory protein levels than those caused by either gene polymorphisms or depression alone, increasing risk of subsequent MACE. Specific aims are to determine 1) whether depression is associated with the risk of MACE; 2) whether inflammatory protein levels during ACS differ between those with and without depression; 3) whether selected genetic polymorphisms are related to the level of inflammatory proteins; 4) whether genetic polymorphisms and depressive symptoms interact to influence the level of inflammatory proteins; and 5) and whether genetic polymorphisms and depressive symptoms interact to influence risk of MACE. Inflammatory proteins and genes include: Interleukin (IL) 6, C-reactive protein (CRP), Tumor Necrosis Factor Alpha (TNFa), E-Selectin (SELE) and Monocyte Chemoattractant Protein-1 (MCP-1). From about 1300 ACS patients, blood samples for genetic and protein work will be collected once shortly after hospital admission before cardiac intervention, and depression will be assessed once within 2-5 days post admission. Occurrence of MACE will be followed for 2 years. Data will be analyzed using logistic regression and survival analysis.