Common Variants in Candidate Genes and Premature MI Risk
Condition: Cardiovascular Diseases; Heart Diseases; Myocardial Infarction
MeSH terms: Cardiovascular Diseases; Heart Diseases; Myocardial Infarction; Infarction
Study type: Observational

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.