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Genetic Mapping of Atherogenic Lipoprotein Phenotypes

Primary Purpose

Atherosclerosis, Cardiovascular Diseases, Heart Diseases

Status
Completed
Phase
Locations
Study Type
Observational
Intervention
Sponsored by
University of Washington
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an observational trial for Atherosclerosis

Eligibility Criteria

undefined - 100 Years (Child, Adult, Older Adult)MaleDoes not accept healthy volunteers

No eligibility criteria

Sites / Locations

    Outcomes

    Primary Outcome Measures

    Secondary Outcome Measures

    Full Information

    First Posted
    May 25, 2000
    Last Updated
    February 8, 2016
    Sponsor
    University of Washington
    Collaborators
    National Heart, Lung, and Blood Institute (NHLBI)
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    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
    background

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    Genetic Mapping of Atherogenic Lipoprotein Phenotypes

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