Trial Information

Study of Chemokine Markers and Genes as Predictors of Cardiovascular Disease

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.