Genetics of Low Density Lipoprotein Subclasses in Hypercholesterolemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00005203
Recruitment Status : Completed
First Posted : May 26, 2000
Last Update Posted : February 10, 2016
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:
University of Washington

Brief Summary:
To perform genetic studies of low density lipoprotein (LDL) subclasses in 160 families in whom the probands had metabolically defined hypercholesterolemia.

Condition or disease
Cardiovascular Diseases Heart Diseases Hypercholesterolemia

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.

Study Type : Observational
Study Start Date : July 1987
Study Completion Date : June 1992

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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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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00005203

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

Publications: Identifier: NCT00005203     History of Changes
Other Study ID Numbers: 1082
R29HL038760 ( U.S. NIH Grant/Contract )
First Posted: May 26, 2000    Key Record Dates
Last Update Posted: February 10, 2016
Last Verified: August 2004

Additional relevant MeSH terms:
Cardiovascular Diseases
Heart Diseases
Lipid Metabolism Disorders
Metabolic Diseases