ENOS AND THE BLOOD LEAD-BLOOD PRESSURE RELATIONSHIP

高血压是心血管疾病的主要原因之一。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高血压的因素。目前尚不清楚铅是如何发挥这种作用的。本研究的目的是利用基于群体的方法和最近报道的内皮型一氧化氮合酶(ENOS)中的Glu298Asp替换多态性，探讨内皮型一氧化氮合酶(ENOS)抑制作为这一效应的机制。具体目的：1)描述eNOS基因Glu298Asp多态与血压的关系。2)描述该队列中eNOS Glu298Asp基因多态性对铅与血压关系的影响。方法：这是一项针对铅接触工人和未接触铅工人的横断面研究。这些工人的血压和铅水平已经被记录下来，并采集了血液样本。血样将进行Glu298Asp多态基因分型。将开发线性回归模型来检验这些工人中铅与血压的关系。我们还将考虑分层分析，观察高血压的优势比。如果eNOS参与了铅引起的血压升高，则患有和不存在Asp变异型eNOS的个体的铅-血压关系(高血压的回归斜率或优势比)应该不同。

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.