Hyperapo B and Coronary Heart Disease

BACKGROUND:

Hyperapo B is a phenotype defined as elevated plasma level of the major apoprotein B of low density lipoproteins in the presence of a normal plasma level of low density lipoprotein cholesterol. It has been demonstrated that hyperapo B is strongly associated with coronary artery disease. In 1984 when the study began, the independence of this association with other risk factors for coronary artery disease such as cigarette smoking, hypertension, and low plasma levels of high density lipoproteins was not known. The study improved knowledge of the pathophysiology of coronary artery disease and of the genetic and biochemical defects of hyperapo B and hypoalphalipoproteinemia.

DESIGN NARRATIVE:

Interviews were conducted and clinical data collected on each index case and spouse, as well as on first degree relatives. Risk factor data included blood pressure, blood lipid levels, obesity, cigarette smoking, fasting blood sugar and diabetes, hormone use and menopause for women, physical activity, personality scores, and family history. Clinical data included the indications for coronary arteriography, history of use of lipid-lowering agents and insulin, presence of corneal arcus, xanthomata, and xanthelasma, and the electrocardiogram.

To determine if the apolipoprotein B gene and the apolipoprotein A1-C3-A4 gene cluster were independent predictors of premature coronary disease, the relation between DNA polymeric sites within the two genes and coronary disease were investigated using cloned DNA fragments as molecular probes. To determine if apolipoprotein B and apolipoprotein A levels aggregated in families and to determine if hyperapo B and hypoalphalipoproteinemia segregated as Mendelian traits, genetic analysis was conducted in the 200 index cases and the 900 first degree relatives. Studies were also conducted on the linkages between hyperapo B and haplotypes of the apolipoprotein B gene, on hyperapo B and the Ag polymorphisms, and on hyperalphalipoproteinemia and haplotypes of the apolipoprotein A1-C3-A4 gene cluster.