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Genetic Mapping of Atherogenic Lipoprotein Phenotypes

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: NCT00005465
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 map the major gene influencing low-density lipoprotein subclass phenotypes, denoted atherogenic lipoprotein (ALP) phenotypes, with a long term goal of cloning the ALP gene and understanding its role in genetic susceptibility to atherosclerosis.

Condition or disease
Atherosclerosis Cardiovascular Diseases Heart Diseases

Detailed Description:


ALP phenotype B (ALP-B), characterized by a predominance of small, dense LDL particles as determined by gradient gel electrophoresis, has been associated with increased risk of myocardial infarction and a constellation of atherogenic lipid and apolipoprotein (apo) changes. Based on complex segregation analysis, ALP-B appeared to be influenced by a single major genetic locus with a dominant mode of inheritance and a common allele frequency. This project was designed to identify a new gene involved in susceptibility to coronary heart disease.


The investigators identified, collected and constructed a repository of immortalized cell lines and lipid and apo measurements from members of families informative for ALP. They tested genes implicated in lipoprotein metabolism as possible candidate ALP genes and used highly informative DNA probes to search the genome for linkage to the ALP gene. They also refined the model for the inheritance of ALP phenotypes and tested for genetic-environmental interactions. Forty informative families were recruited for the repository. The families were identified through two sources of probands: former participants in a cholesterol-lowering diet study and patients seen at the lipid clinics at the University of Washington. Each participating family member completed a medical history questionnaire and provided a blood sample for ALP phenotype determination, for DNA studies, and for lipid and apo measurements. Linkage studies and LOD score analyses began with a candidate gene approach, and continued by using DNA probes that revealed restriction fragment length polymorphisms (RFLPs) to search the genome for linkage to the ALP gene. When a linkage was found, ALP genotype information was used to refine the statistical model describing the inheritance of ALP phenotypes, and to evaluate genetic-environmental interactions involving lipid and apo levels and environmental and behavioral factors.

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Study Type : Observational
Study Start Date : August 1991
Study Completion Date : July 1996

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 100 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
No eligibility criteria


Layout table for additonal information Identifier: NCT00005465    
Other Study ID Numbers: 4909
R01HL046880 ( U.S. NIH Grant/Contract )
First Posted: May 26, 2000    Key Record Dates
Last Update Posted: February 10, 2016
Last Verified: May 2001
Additional relevant MeSH terms:
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Heart Diseases
Cardiovascular Diseases
Arterial Occlusive Diseases
Vascular Diseases