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Genetics of Low Density Lipoprotein Subclasses in Hypercholesterolemia

This study has been completed.
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:
University of Washington Identifier:
First received: May 25, 2000
Last updated: February 8, 2016
Last verified: August 2004
To perform genetic studies of low density lipoprotein (LDL) subclasses in 160 families in whom the probands had metabolically defined hypercholesterolemia.

Cardiovascular Diseases Heart Diseases Hypercholesterolemia

Study Type: Observational

Resource links provided by NLM:

Further study details as provided by University of Washington:

Study Start Date: July 1987
Estimated Study Completion Date: June 1992
Detailed Description:


Low density lipoprotein cholesterol has been convincingly established as a major coronary heart disease risk factor by many epidemiologic studies, clinical trials, and experimental studies. A strong inverse association exists between high density lipoprotein cholesterol and coronary heart disease. However, the status of very low density lipoprotein (VLDL) cholesterol and plasma triglyceride levels as independent risk factors for cardiovascular disease is less clear. Case control studies have shown a positive association between coronary heart disease and plasma levels of apoprotein B, the major protein on LDL particles, and an inverse relationship with apoprotein AI, the primary protein constituent of HDL particles. In fact, it has been proposed that plasma levels of the apoproteins may be stronger risk factors than lipid levels. Thus, understanding the mechanisms underlying variations in both lipoprotein and apoprotein levels among individuals is essential to elucidating the etiology of coronary heart disease in the general population.

Cardiovascular disease is also known to cluster in families, and this may be related to the clustering of lipid and lipoprotein levels among family members. A review suggested that the familial aggregation of heart disease may be primarily a reflection of the familial aggregation of known risk factors, including cholesterol levels. The work of Goldstein and Brown on familial hypercholesterolemia demonstrated that genetic control of lipoprotein metabolism can play a causative role in the development of atherosclerosis. However, familial hypercholesterolemia is a relatively rare disorder: the prevalence of heterozygotes is estimated to be 1 in 500, homozygotes 1 in a million. In 1987, little was understood about more common genetic contributions to lipid and lipoprotein abnormalities leading to the familial aggregation of coronary heart disease.


The design was that of a cross-sectional family study. The recruitment and screening of probands were conducted over a four-year period at the University of Texas at Dallas under separate funding. The recruitment and screening of first-degree relatives were carried out at Berkeley. Blood samples were obtained from relatives for LDL subclass analysis and for lipid and apoprotein determination. An interview was conducted to obtain demographic information and information on behavioral and environmental risk factors such as smoking, exercise, and diet. The data were used to determine whether LDL subclasses were genetically controlled in families with hypercholesterolemia due to overproduction of LDL or defective clearance of LDL particles. Segregation analysis of LDL subclasses in these two types of families was performed to search for a single major genetic locus and to simultaneously test for the influence of polygenes and environmental effects. The relationships between the LDL subclass phenotype characterized by a predominance of small, dense LDL and overproduction of apoprotein B and LDL clearance defects were investigated in family members. A determination was made as to whether an age-of-onset effect existed for the expression of LDL subclass phenotypes. Genetic-environmental interactions were also studied.


Ages Eligible for Study:   up to 100 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
No eligibility criteria
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Please refer to this study by its identifier: NCT00005203

Sponsors and Collaborators
University of Washington
National Heart, Lung, and Blood Institute (NHLBI)
OverallOfficial: Melissa Austin University of Washington
  More Information

Publications: Identifier: NCT00005203     History of Changes
Other Study ID Numbers: 1082
R29HL038760 ( U.S. NIH Grant/Contract )
Study First Received: May 25, 2000
Last Updated: February 8, 2016

Additional relevant MeSH terms:
Cardiovascular Diseases
Heart Diseases
Lipid Metabolism Disorders
Metabolic Diseases processed this record on July 21, 2017