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

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 这项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。一般的假设是，与仅表达可变危险因素的受试者相比，心血管疾病风险降低干预在具有高炎症性表型和相关基因的受试者中效果较差。为了验证这一假设，我们设计了三个具体目标： 具体目标1：确定心血管疾病高危人群唾液浓度与血清炎症标志物(IL-1、IL-6、肿瘤坏死因子和C反应蛋白)浓度的关系。 具体目标2：在基线水平C反应蛋白升高和降低的受试者中，确定降低心血管疾病风险的行为干预措施对唾液和血清炎症生物标记物以及不良心血管事件风险的影响。 具体目标3：阐明预测心血管疾病风险降低干预反应的基因型别，以及高炎症表型的任何效应改变。 这是一个杠杆研究项目，与人权事务管理局资助的“肯塔基州农村的心脏健康”项目相结合。在HEART Health研究中，从四个农村社区站点招募了1000名被诊断患有或具有两种或两种以上心血管疾病风险因素的成年人。关于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，正在收集基线和干预后立即和延长的数据。 对于杠杆式研究，在每个时间点收集的额外数据包括血清和唾液样本，以检测全身炎症的生物标志物，包括C-反应蛋白(CRP)、白细胞介素1(IL)-1、白介素6和肿瘤坏死因子α(TNF)。唾液也被收集用于DNA分析，以确定目标基因变体和炎症介质之间的联系，以及它们对降低心血管疾病风险干预措施的个体反应差异的贡献。牙周状况在基线时进行评估，以控制混杂。 研究对象将被分配到两组中的一组。在第一组中，300名基线hs-CRP值为3 mg/L的受试者将被纳入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进行匹配，300名参与者的基线hsCRP水平为1 mg/L，代表低炎症表型。这项研究将仅限于高加索人，因为肯塔基州农村人口的大多数是高加索人，研究种族和民族的影响的人数将不足。

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.