Genetics of CRP in Families With Myocardial Infarction
To investigate the genetics of C reactive protein in families with myocardial infarction.
|Study Design:||Observational Model: Case Control
Time Perspective: Cross-Sectional
- Association of markers with cardiovascular event [ Time Frame: Event recorded at time of recruitment ] [ Designated as safety issue: No ]
Biospecimen Retention: Samples With DNA
i.) Blood: A blood sample (30 cc, ~2 tablespoons) will be drawn. This will take place in the catheterization lab at the end of the catheterization procedure or by using standard venipuncture technique during a clinic visit or at community outreach events when feasible.
ii.) Buccal Swab: The participant uses specially prepared cotton swabs (called buccal swabs) to rub in a circular motion on the inside of both cheeks. The swabs collect cheek cells that can be processed to obtain DNA.
iii.) Saliva: A saliva sample is obtained by having the participant spit in a special vial specifically designed for genetic testing. The participant will continue to spit into the vial until it contains 2 ml (about 1 teaspoon) of saliva.
|Study Start Date:||July 2003|
|Study Completion Date:||June 2008|
|Primary Completion Date:||June 2008 (Final data collection date for primary outcome measure)|
Families with MI
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
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00064519
|Principal Investigator:||Ulrich Broeckel||Medical College of Wisconsin|