Genetic Mapping of Atherogenic Lipoprotein Phenotypes
Primary Purpose
Atherosclerosis, Cardiovascular Diseases, Heart Diseases
Status
Completed
Phase
Locations
Study Type
Observational
Intervention
Sponsored by

About this trial
This is an observational trial for Atherosclerosis
Eligibility Criteria
No eligibility criteria
Sites / Locations
Outcomes
Primary Outcome Measures
Secondary Outcome Measures
Full Information
NCT ID
NCT00005465
First Posted
May 25, 2000
Last Updated
February 8, 2016
Sponsor
University of Washington
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
1. Study Identification
Unique Protocol Identification Number
NCT00005465
Brief Title
Genetic Mapping of Atherogenic Lipoprotein Phenotypes
Study Type
Observational
2. Study Status
Record Verification Date
May 2001
Overall Recruitment Status
Completed
Study Start Date
August 1991 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
July 1996 (undefined)
3. Sponsor/Collaborators
Name of the Sponsor
University of Washington
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
4. Oversight
5. Study Description
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.
Detailed Description
BACKGROUND:
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.
DESIGN NARRATIVE:
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atherosclerosis, Cardiovascular Diseases, Heart Diseases
7. Study Design
10. Eligibility
Sex
Male
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
No eligibility criteria
12. IPD Sharing Statement
Citations:
PubMed Identifier
9463319
Citation
Austin MA, Talmud PJ, Luong LA, Haddad L, Day IN, Newman B, Edwards KL, Krauss RM, Humphries SE. Candidate-gene studies of the atherogenic lipoprotein phenotype: a sib-pair linkage analysis of DZ women twins. Am J Hum Genet. 1998 Feb;62(2):406-19. doi: 10.1086/301712.
Results Reference
background
PubMed Identifier
8949979
Citation
Austin MA. Genetic epidemiology of dyslipidaemia and atherosclerosis. Ann Med. 1996 Oct;28(5):459-63. doi: 10.3109/07853899608999108.
Results Reference
background
PubMed Identifier
8818515
Citation
Austin MA, Edwards KL. Small, dense low density lipoproteins, the insulin resistance syndrome and noninsulin-dependent diabetes. Curr Opin Lipidol. 1996 Jun;7(3):167-71. doi: 10.1097/00041433-199606000-00010.
Results Reference
background
PubMed Identifier
7550534
Citation
Austin MA, Selby JV. LDL subclass phenotypes and the risk factors of the insulin resistance syndrome. Int J Obes Relat Metab Disord. 1995 May;19 Suppl 1:S22-6.
Results Reference
background
PubMed Identifier
7712044
Citation
Austin MA, Hokanson JE, Brunzell JD. Characterization of low-density lipoprotein subclasses: methodologic approaches and clinical relevance. Curr Opin Lipidol. 1994 Dec;5(6):395-403. doi: 10.1097/00041433-199412000-00002.
Results Reference
background
PubMed Identifier
7894041
Citation
Austin MA. Small, dense low-density lipoprotein as a risk factor for coronary heart disease. Int J Clin Lab Res. 1994;24(4):187-92. doi: 10.1007/BF02592460.
Results Reference
background
PubMed Identifier
7988081
Citation
Austin MA. Genetic and environmental influences on LDL subclass phenotypes. Clin Genet. 1994 Jul;46(1 Spec No):64-70. doi: 10.1111/j.1399-0004.1994.tb04204.x.
Results Reference
background
PubMed Identifier
8283937
Citation
Austin MA, Hokanson JE. Epidemiology of triglycerides, small dense low-density lipoprotein, and lipoprotein(a) as risk factors for coronary heart disease. Med Clin North Am. 1994 Jan;78(1):99-115. doi: 10.1016/s0025-7125(16)30178-x.
Results Reference
background
PubMed Identifier
8314067
Citation
Austin MA, Jarvik GP, Hokanson JE, Edwards K. Complex segregation analysis of LDL peak particle diameter. Genet Epidemiol. 1993;10(6):599-604. doi: 10.1002/gepi.1370100645.
Results Reference
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Genetic Mapping of Atherogenic Lipoprotein Phenotypes
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