Genetics of CRP in Families With Myocardial Infarction

Medical College of Wisconsin

Status: Completed

Conditions: Myocardial Infarction; Cardiovascular Diseases; Heart Diseases; Coronary Disease

Study type: Observational

Funder types: Other; NIH

Identifiers

NCT00064519

R01HL074321 (U.S. NIH Grant/Contract)

1225

Details and patient eligibility

About

To investigate the genetics of C reactive protein in families with myocardial infarction.

Full description

BACKGROUND:

Coronary artery disease (CAD) and myocardial infarction (MI) are the leading causes of death in the Western world. Numerous epidemiological studies have demonstrated the impact of various risk factors, such as arterial hypertension, hypercholesterolemia and diabetes mellitus. While these risk factors are partly under genetic control, a positive family history remains an additional independent predictor of CAD, suggesting the presence of as yet unidentified susceptibility loci. Given the enormous public health burden of CAD, there is significant interest in identifying its specific genetic foundations. As intensive experimental investigations continue, the inflammatory component of the disease process leading to atherosclerosis evolves as a key aspect in the disease process. Recent evidence demonstrates that systemic markers of inflammation such as C reactive protein (CRP) can predict those at high risk of coronary events. CRP emerges with much attention as both a diagnostic marker and therapeutic target with serum levels determined to a significant extent by genetic factors.

DESIGN NARRATIVE:

To elucidate the genetic basis of the inflammatory component of myocardial infarction and the regulation of C reactive protein, a gene function oriented evaluation of candidate genes will be conducted. Therefore the specific aims are as follows, 1. Identify positional candidate genes within regions identified for MI and CRP which are functionally related to inflammation and inflammatory processes. Sequence variation in selected candidate genes will be identified. 2. Evaluate the effect of these variants with regard to MI and CRP in two different ethnic populations: a family set of European Caucasians and a population-based, Hispanic family dataset. The role of CRP will be evaluated as a predictor of cardiovascular events in the study populations. Since clinical follow up data are available on both study populations, the extent to which CRP contributes to an increased risk for cardiovascular events will be analyzed.

Enrollment: 1,406 patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

1. First Part DNA Collection

   a.) Inclusion Criteria i.) Being 18 years of age or older. ii.) Having had a cardiac catheterization procedure performed or undergoing one in the near future.

   iii.) A person having a family history of coronary artery disease and having at least one family member that has had a cardiac catheterization that is willing to participate.

   iv.) Having coronary artery (right, left main, circumflex, marginal and/or diagonal) blockage in a specific portion of the vessel (ostial, proximal, mid and/or distal).

   b.) Exclusion Criteria i.) Having had a bone marrow transplant.

2. Second Part Coronary Collateralization and Extended Phenotyping a.) Inclusion Criteria i.) Having participated in DNA collection. ii.) Having at least one coronary artery with 100% blockage or iii.) Having normal coronary arteries with no blockage b.) Exclusion Criteria i.) Having received a diagnosis and treatment for kidney disease, cancer, myocardial infarction within the last three (3) months.

ii.) Having a heart transplant.

Trial design

1,406 participants in 1 patient group

Families with MI

Description:

In conjunction with collaborators in Germany, we have established one of the largest collections of families with MI, comprising 1,406 individuals in 513 Western-European families. Based on this collection, our total genome scan and linkage analysis has identified a region on chromosome 14 with a significant linkage signal for myocardial infarction (LOD = 3.9, pointwise P = 0.00015, genome-wide P \< 0.05)5. Preliminary results from an association study in a subset of these families has identified a small set of single nucleotide polymorphisms (SNPs) within candidate genes in this region as being suggestively associated with MI. No drugs are to be administre