Common Variants in Candidate Genes and Premature MI Risk

NCT ID: NCT00005488

Last Updated: 2016-02-10

Basic Information

• Recruitment Status: COMPLETED
• Study Classification: OBSERVATIONAL
• Study Start Date: 1998-07-31
• Study Completion Date: 2002-08-31

Brief Summary

To examine the impact of an interaction between common genetic susceptibility markers and environmental exposures on risk for early onset myocardial infarction in cases with myocardial infarction and matching controls.

Detailed Description

BACKGROUND:

Inherited factors play a role in the pathogenesis of myocardial infarction (MI), and there is growing interest in identifying common genetic susceptibility markers that interact with common environmental exposures to contribute to the occurrence of myocardial infarction (MI) in the population.

DESIGN NARRATIVE:

The study had a case-control design. The preliminary data addressed the contribution of common genetic and environmental factors to the risk of MI among women under 45 years of age. Those data showed that common polymorphisms in genes coding for two clotting factors, coagulation Factor V and coagulation Factor II, were risk factors for MI only among cigarette smokers in this sample. These relationships, and others observed, provided strong evidence of gene-environment interactions between thrombotic and atherosclerotic factors in early-onset MI. One intent was to determine whether the risk of early-onset MI was related to interactions between environmental factors (e.g., cigarette smoking, exercise, alcohol consumption) and common polymorphisms in genes coding for thrombotic factors (coagulation Factor V, coagulation Factor II, plasminogen activator inhibitor-1, and beta-fibrinogen) and atherosclerotic factors (the adhesion molecule E-selectin and metalloproteinase stromelysin-1; the lipid metabolism enzymes paraoxinase, lipoprotein lipase, cholesterol ester transfer protein; and the apolipoproteins apolipoprotein E and apolipoprotein B). Additionally, there were plans to determine whether the risk of early-onset MI was related to interactions between plasma lipoprotein(a) levels (which were largely genetically determined) and environmental risk factors and/or polymorphisms in the candidate genes. Interactions among candidate polymorphisms were also assessed.

Newly-diagnosed cases of MI and controls will be interviewed in person to assess medical and behavioral characteristics related to MI risk. A venous blood sample will be obtained and processed into aliquots of plasma and white cells. DNA extracted from the white cells will be tested using the polymerase chain reaction (PCR), PCR/restriction fragment length polymorphisms (RFLP), and oligonucleotide ligation assays to determine the genotypes of interest. Plasma will be tested for lipid, lipoprotein, and homocysteine concentrations. Analyses will address both the overall association between the genotypes and MI risk, along with posited gene-environment and gene-gene interactions.

Conditions

Cardiovascular Diseases; Heart Diseases; Myocardial Infarction

Eligibility Criteria

Inclusion Criteria

No eligibility criteria

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 59 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of Washington

OTHER

Sponsor Role: lead

Principal Investigators

Stephen Schwartz

Role:

University of Washington

Other Identifiers

R01HL056931

Identifier Type: NIH

Identifier Source: secondary_id

View Link

5004

Identifier Type: -

Identifier Source: org_study_id