Estrogen Receptor Variants, HDL, and Atherosclerosis
Condition: Cardiovascular Diseases; Atherosclerosis; Coronary Arteriosclerosis; Heart Diseases
MeSH terms: Cardiovascular Diseases; Heart Diseases; Atherosclerosis; Arteriosclerosis; Coronary Artery Disease; Myocardial Ischemia
Study type: Observational

Summary: 
      To measure the association between estrogen receptor variants and the extent of
      atherosclerosis in the thoracic and abdominal aorta and the right coronary artery in subjects
      in the PDAY study.
    

Detailed description: 
      BACKGROUND:

      Increased levels of HDL cholesterol are associated with lower rates of clinical and anatomic
      atherosclerosis, even in adolescents and young adults. In premenopausal women,
      estrogen-associated increases in HDL may account for their low rates of coronary heart
      disease (CHD) events. Recently, a sequence variant in the estrogen receptor-alpha (ER-alpha)
      gene, ER-alpha IVS1-397 T/C), has been linked to twofold greater increases in HDL cholesterol
      in response to hormone replacement therapy (HRT). However, it remains unclear whether this
      sequence variant also augments HDL levels in the setting of premenopausal estrogen exposure
      and whether such differences translate into greater reductions in atherosclerosis risk. The
      study uses the cohort of the Pathobiology of Atherosclerosis in Youth (PDAY) study, a large
      cross-sectional autopsy study of the extent of atherosclerosis in subjects aged 15 to 34
      years. The detailed descriptions of atherosclerotic lesions, combined with data on
      cardiovascular risk factors and access to tissue for DNA extraction, makes this an ideal
      cohort in which to examine the association between ER-alpha IVS1-397 genotypes, HDL levels,
      and development of early atherosclerosis.

      DESIGN NARRATIVE:

      The overall goal for this study is to measure the association between the estrogen receptor
      (ER- IVS1-401 T/C) polymorphism and extent of abdominal aorta, thoracic artery, and right
      coronary artery atherosclerosis in Pathobiological Determinants of Atherosclerosis in Youth
      (PDAY) subjects. The investigators will use DNA extracted from liver specimens in order to
      measure the ER polymorphisms. The extent of atherosclerosis will be defined as the percent of
      intimal area involved with fatty streaks or raised lesions, using previously established PDAY
      definitions. However, percent involvement of fatty streaks alone and the percent involvement
      of the individual components of raised lesions (fibrous plaques, complicated lesions, and
      calcified lesions) will be analyzed separately. Available data on risk factors (smoking,
      diabetes, hyperlipidemia, hypertension) will permit reducing confounding of the results by
      allowing adjustments for effects of the major risk factors for coronary heart disease. The
      Department of Pathology at Louisiana State University Health Sciences Center (LSUHSC) has
      been designated by the National Heart, Lung and Blood Institute to centralize, maintain, and
      distribute the valuable material collected through the combined efforts of the cooperating
      institutions for further studies in atherosclerosis. LSUHSC will provide DNA for polymorphism
      analysis and assist in data analysis. Polymorphism determination will occur at Wake Forest.