ENOS AND THE BLOOD LEAD-BLOOD PRESSURE RELATIONSHIP

原发性高血压是导致心血管疾病的主要原因。其病因被认为涉及遗传和环境因素。血铅水平升高已被认为是导致原发性高血压的一个因素。目前尚不清楚铅是如何产生这种影响的。本研究的目的是利用基于群体的方法和最近报道的eNOS中Glu298Asp取代多态性，考虑内皮型一氧化氮合酶（eNOS）抑制作为这种效应的机制。具体目的：1)描述该队列中eNOS Glu298Asp多态性与血压的关系。2)描述该队列中eNOS Glu298Asp多态性对铅与血压关系的影响。方法：这将是一项铅暴露工人和未暴露对照者的横断面研究。对这些工人的血压和铅含量进行了记录，并采集了血液样本。将对血样进行Glu298Asp多态性基因分型。将建立线性回归模型来检验这些工人的铅和血压的关系。我们还将考虑分层分析，观察高血压的优势比。如果eNOS与铅引起的血压升高有关，那么对于患有和不患有asp变异性eNOS的个体，铅-血压关系（回归斜率或高血压的优势比）应该是不同的。

Essential hypertension is a major cause of cardiovascular disease. Its etiologies are thought to involve both genetic and environmental factors. Elevated blood lead levels have been indicated as contributing factor in essential hypertension. It is unclear how lead exerts this effect. The purpose of this investigation is to consider endothelial nitric oxide synthase (eNOS) inhibition as a mechanism for this effect, using a population based approach and a recently reported Glu298Asp substitution polymorphism in eNOS. Specific Aims: 1) Describe the relation of the eNOS Glu298Asp polymorphism and blood pressure in this cohort. 2) Describe how the relation of lead and blood pressure varies by the eNOS Glu298Asp polymorphism in this cohort. Methods: This will be a cross-sectional study of lead exposed workers and unexposed controls. Blood pressure and lead levels in these workers have been recorded, and blood samples have been taken. The blood samples will be genotyped for the Glu298Asp polymorphism. Linear regression models will be developed to examine the relation of lead and blood pressure in these workers. We will also consider stratified analyses, looking at odds ratios of hypertension. If eNOS is involved in lead induced increases in blood pressure, the lead-blood pressure relationship (the regression slopes or the odds ratios for hypertension) should different for individuals with and without Asp-variant eNOS.