Genetic Predictors of Cardiovascular Disease

Overview

This study, conducted in collaboration with the Johns Hopkins University School of Medicine, will explore the genetic influences on susceptibility to atherosclerotic cardiovascular disease (ASCVD). Atherosclerosis is a chronic narrowing of the arteries caused by an incremental buildup of fatty substances on the linings of walls of arteries. This study will examine the role of genes related to the inflammatory process on the incidence of ASCVD and on levels of chemokines (proteins involved in inflammation). DNA samples, chemokines levels and relevant clinical data from patients enrolled in Johns Hopkins's sibling and family heart studies are analyzed for specific gene markers. The studies include: Nurse Model in Black Families at Risk for Heart Disease; Genotypic Determinants of Aspirin Response in High Risk Families; and Coronary Disease Detection by Thallium SPECT and Fast CT. All of the enrolled patients have consented to have their DNA used for testing of genetic factors that may predict cardiovascular disease and do not contain patient identifier information.

Background: Atherosclerosis is a chronic inflammatory disease classically triggered by hypertension, diabetes, smoking and elevated cholesterol. It is hypothesized that genetic predisposition plays a crucial role in an individual's susceptibility to these risk factors with Single Nucleotide Polymorphisms (SNPs) being identified as functional mediators of key inflammatory genes. Objectives: To determine the frequency of haplotypes of SNP combinations in the proximal promoter region of MCP-1, the MCP-3 gene, and eotaxin gene in patients with risk factors for CVD and their siblings. To determine the MCP-1 levels in an affected population with Coronary artery disease and their siblings and certain haplotypes to determine a functional association between MCP-1 levels and haplotype frequency. Eligibility: Eligibility criteria for enrollment in sib and family studies included: 1) having a sib or 1st degree family member with heart disease, 2) ability to give inform consent to participate in the study, 3) age 18 years or older, 4) ability to speak English or Spanish. The entire set of 2,000 samples available to the LDG will be analyzed. No subject will be excluded. Design: DNAs derived from properly consented subjects enrolled in three protocols sponsored by the Johns Hopkins Heart Study will be sent to the LGD and used to test specific markers in the MCP-1, MCP-3, and eotaxin chemokine family located in the C-C chemokine cluster on chromosome17q11.2. A minimum of 11 SNPs will be examined. Sib-pair analysis will be utilized to identify associated markers. Linear regressions will be used to analyze associations between genetic variations and chemokine levels. Haplotype will be assigned to unrelated individuals using the maximum likelihood approach. The DNA samples, chemokine levels, and relevant clinical data provided by John Hopkins University School of Medicine will be coded and linked. Following this study, the DNAs will be maintained in our repository and curated through our central Laboratory database. Loss or destruction of these samples will be annotated to our database and cannot impact the study participants in any way. We understand that studies subsequent to the completion of this protocol will require additional OHSR/IRB approval prior to commencement.