Genetic Markers of CHD Risk in Men and Women
Condition: Cardiovascular Diseases; Coronary Disease; Heart Diseases; Myocardial Infarction; Inflammation
MeSH terms: Cardiovascular Diseases; Heart Diseases; Myocardial Infarction; Coronary Disease; Inflammation; Infarction
Study type: Observational

Summary: 
      To investigate the association of selected genetic markers of inflammation and endothelial
      activation with the occurrence of non-fatal acute myocardial infarction (MI).
    

Detailed description: 
      BACKGROUND:

      Coronary artery disease is a major cause of death and disability in westernized societies,
      and is growing in importance in countries with emerging economies. Inflammation and
      endothelial dysfunction are now recognized as important contributors to coronary artery
      disease. However, the genetic basis and specific genes involved in the expression of the
      hyperinflammatory phenotype are not yet well-understood. Identification and further
      characterization of variation in candidate loci that are associated with coronary artery
      disease would contribute to the understanding of the genetic basis underlying acute
      myocardial infarction, and may provide novel pathways for prevention and treatment.

      DESIGN NARRATIVE:

      This case-control study will determine whether the variability in several genes that
      influence inflammation and endothelial dysfunction is related to the odds of myocardial
      infarction (MI) among 700 men and 229 postmenopausal women from the Western New York Health
      Study. The study performs the following: 1) To test the hypothesis that cases of acute MI
      will have a higher frequency of specific haplotypes at the C-reactive protein locus composed
      of alleles associated with higher levels of CRP production (-732G/A), 1059G/C, and +1444C/T)
      than matched controls. MI cases will have a greater frequency of haplotypes composed of
      alleles associated with higher levels of interleukin (IL) production, specifically IL-6
      production (-597G/A, -572G/C, and -174G/C) than controls, and a lower frequency of specific
      haplotypes in the IL1A/IL1 BILL1RN gene region; 2) cases will have a higher frequency of
      alleles and haplotypes for specific functional polymorphisms of the E-selectin gene (128R and
      G98T) than controls; 3) to utilize DNA pooling strategy for rapid screening of large numbers
      of single nucleotide polymorphisms (SNPs) in 29 candidate genes in relevant biological
      pathways and test selected loci for association with risk of acute MI; 4) for those loci with
      evidence of association, to identify haplotype tagging single nucleotide polymorphisms
      (htSNPs) that capture the variation at each locus and test for association between these SNPs
      and haplotypes and risk of MI. Secondary aims will a) explore the above associations among
      men with premature MI (55 years of age or less) and b) explore gene- gene and gene-
      environment interactions. MI case subjects were identified from hospital record review in
      Erie and Niagara counties (95% of all eligible cases, ICD9 410-410.9) an average of 4 months
      post MI. They were interviewed and examined in 1996-2001. Control subjects were randomly
      selected from the same counties (59.5% response rate) and had a contemporaneous clinical
      exam. Controls will be individually matched to cases by age, sex, and ethnicity.