GENE-ENVIRONMENT INTERACTIONS REG CVD INFL/SUCCESS OF BEHAVIORAL THERAPIES

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 本研究的总体目标是检查炎症基因型与心血管风险降低干预对全身炎症的影响之间的关系。一般假设是，CVD风险降低干预措施在具有高度炎症表型和相关基因型的受试者中的有效性低于仅表达可变风险因子的受试者。为检验这一假设，设计了三个具体目标： 具体目标1：确定有CVD风险或患有CVD的人中选定的炎症生物标志物（IL-1、IL-6、TNF和CRP）的唾液和血清浓度之间的关系。 具体目标二：确定行为CVD风险降低干预对基线时CRP升高和低水平受试者的唾液和血清炎症生物标志物以及不良心血管事件风险的影响。 具体目标3：阐明预测CVD风险降低干预反应的基因型和高炎症表型的任何效应改变。 这是一个杠杆研究项目，与HRSA资助的“肯塔基州农村心脏健康”项目相结合。在心脏健康研究中，从四个农村社区招募了1000名被诊断患有或有两个或两个以上CVD风险因素的成年人。心血管疾病风险因素的数据，包括血压，血脂，糖尿病，吸烟和其他生活方式因素正在收集基线和即时和扩展后干预。 对于杠杆研究，在每个时间点收集的额外数据包括血清和唾液样本标本，以检查炎症的全身生物标志物，包括C反应蛋白（CRP）、白细胞介素（IL）-1、IL-6和肿瘤坏死因子α（TNF？）。还收集唾液进行DNA分析，以确定靶向基因变异和炎症介质之间的关联，以及它们对降低CVD风险干预措施的个体反应变化的贡献。在基线时评估牙周病状态以控制混杂因素。 研究受试者将被分配到两组之一。在第一组中，将招募300名基线hs-CRP为3 mg/L的参与者作为高炎症表型的代表。这些受试者将在年龄、性别、糖尿病诊断和吸烟状况方面与300名基线hsCRP水平为1 mg/L（代表低炎症表型）的受试者相匹配。本研究将仅限于白人，因为肯塔基州农村的大多数人口为白人，并且没有足够的数量可用于研究人种和种族的影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The overall goal of this study is to examine the relationship between inflammatory genotype and the effects of a cardiovascular risk-reduction intervention on systemic inflammation. The general hypothesis is that a CVD risk reduction intervention will be less effective in subjects with a hyper-inflammatory phenotype and associated genotype than in subjects that express mutable risk factors alone. Three specific aims have been designed to test this hypothesis: Specific Aim 1: Determine the relationship between salivary and serum concentrations of selected inflammatory biomarkers (IL-1¿, IL-6, TNF¿, and CRP) in persons at-risk for or with CVD. Specific Aim 2: Determine the effect of a behavioral CVD risk reduction intervention on salivary and serum biomarkers of inflammation and risk for adverse cardiovascular events in subjects with elevated and low CRP at baseline. Specific Aim 3: Elucidate genotypes predictive of the response to the CVD risk reduction intervention and any effect modification by high inflammatory phenotype. This is a leveraged research project integrated with the HRSA-funded "HeartHealth in Rural Kentucky" project. For the HeartHealth study, 1000 adults diagnosed with or having two or more risk factors for CVD are being recruited from four rural community-based sites. Data on CVD risk factors including blood pressure, lipid profile, diabetes, smoking and other lifestyle factors is being collected at baseline and immediate and extended post-intervention. For the leveraged study, additional data collected at each time point includes serum and saliva samples specimens to examine systemic biomarkers of inflammation including C-reactive protein (CRP), interleukin (IL)-1¿, IL-6, and, tumor necrosis factor alpha (TNF¿). Saliva is also collected for DNA analysis to determine associations between targeted gene variants and inflammatory mediators and their contribution to variations in individual response to CVD risk-reducing interventions. Periodontal status is assessed at baseline to control for confounding. Study subjects will be allocated to one of two groups. In group one, 300 participants with a baseline hs-CRP of 3mg/L will be enrolled as representative of a high inflammatory phenotype. These subjects will be matched on age, gender, diagnosis of diabetes, and smoking status with 300 participants with a baseline hsCRP level of 1mg/L, representing a low inflammatory phenotype. The study will be restricted to Caucasians, as the majority of the rural Kentucky population is Caucasian and insufficient numbers will be available to study effects of race and ethnicity.