Epidemiology of Genetic Factors in Lipid Metabolism
Condition: Cardiovascular Diseases; Heart Diseases; Atherosclerosis
MeSH terms: Cardiovascular Diseases; Heart Diseases; Atherosclerosis
Study type: Observational

Summary: 
      To investigate the genetics and epidemiology of fasting and postprandial lipid, lipoprotein,
      and apolipoprotein levels.
    

Detailed description: 
      BACKGROUND:

      Altered plasma lipid, lipoprotein, and apolipoprotein levels are associated with the
      occurrence of coronary heart disease, non-insulin dependent diabetes, and gallbladder
      disease. Although there are many other environmental and biological correlates, clinical,
      epidemiological, and experimental lines of evidence indicate that lipid metabolism has a
      central role in the development of coronary heart disease. Evidence pointing to the
      association between measures of lipid metabolism and other chronic diseases is no less
      compelling. Non-insulin dependent diabetes mellitus exhibits both the diagnostic abnormal
      carbohydrate utilization, and altered lipid metabolism. The hypothesis that abnormal lipid
      metabolism may be causally involved in gallbladder disease is suggested by the presence of
      cholesterol saturated bile several years prior to the onset of clinically definable
      gallstones.

      Biometrical genetic studies have established that a significant proportion of the fasting
      plasma lipid, lipoprotein, and apolipoprotein levels is attributable to genetic differences
      among individuals. Although these studies indicate that polygenetic variability is
      contributing, they do not yield information about specific candidate genes whose products are
      involved in the metabolism of the phenotype of interest. Recent advances in molecular biology
      enable one to measure genetic variability at candidate loci for several risk factors for the
      common chronic diseases. With this information the contribution of specific candidate genes
      to polygenetic and phenotypic variability can be estimated. Estimating the effects of
      specific candidate loci will facilitate the investigation of the interaction between genetic
      and environmental factors. This study focussed on restriction fragment length polymorphisms
      in and around the apolipoprotein B gene and on the apolipoprotein E protein polymorphism. The
      apolipoprotein B and apolipoprotein E genes were selected because of their central role in
      lipid metabolism and interaction with dietary factors.

      DESIGN NARRATIVE:

      Using data and blood samples from the 75 nuclear families of Nancy, a determination was made
      of the effects of apolipoprotein B and E genes on fasting levels of total cholesterol and
      triglycerides, LDL-cholesterol, HDL-cholesterol, HDL2-cholesterol, HDL3-cholesterol, apo A-I,
      apo-B, apo C-III, and apo-E. Genetic variability was directly assessed by DNA restriction
      site variability in the apolipoprotein B gene and by measuring the apolipoprotein E
      polymorphism. Data collected from these families permitted the partitioning of the effects of
      the apolipoprotein B and E genes from the overall polygenetic and phenotypic variance of the
      measured lipids, lipoproteins, and apolipoproteins.

      Fasting and postprandial lipids, lipoproteins, and apolipoproteins were obtained from 100
      Mexican-American women. A determination was made of the effects of apolipoprotein E and B
      genes, disease status, age, and their interactions on fasting and postprandial lipid
      metabolism.
    

Observational model: Case-Only
Time perspective: Cross-Sectional
Study population: 
        Sample of 75 nuclear families from Nancy France. Sample of 100 unrelated Mexican-Americans
        from Laredo, Texas.
      
Biospecimen description: 
      Genetic variability will be directly assessed by DNA restriction site variability in the
      apolipoprotein B gene and by measuring the apolipoprotein E polymorphism. These analyses will
      be carried out on a sample of 75 nuclear families from Nancy France.

      Both fasting and postprandial lipids, lipoproteins, an apolipoproteins will be obtained on a
      sample of 100 unrelated Mexican-Americans from Laredo, Texas.