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

University Of Kentucky, Lexington KY

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Abstract

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[unreadable], IL-6, TNF[unreadable], 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[unreadable], IL-6, and, tumor necrosis factor alpha (TNF[unreadable]). 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.