Cardiovascular DiseasesNCT00005203
Genetics of Low Density Lipoprotein Subclasses in Hypercholesterolemia
An observational study of Cardiovascular Diseases and Heart Diseases, run by University of Washington.
Trial summary
To perform genetic studies of low density lipoprotein (LDL) subclasses in 160 families in whom the probands had metabolically defined hypercholesterolemia. Read more about this study
- Who is it for?
- Ages Up to 100 years, men only
- Conditions the study is for
- Cardiovascular Diseases, Heart Diseases, Hypercholesterolemia
- How many people
- Not given
- Where
- No sites listed yet
- Study dates
- Jul 1987to Jun 1992
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 100 years
- Men only
- No healthy volunteers
- Child, Adult, Older adult
No eligibility criteria
About this study
To perform genetic studies of low density lipoprotein (LDL) subclasses in 160 families in whom the probands had metabolically defined hypercholesterolemia.
Read the detailed description
BACKGROUND:
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.
DESIGN NARRATIVE:
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.
- Medical subject headings
- Cardiovascular Diseases, Heart Diseases, Hypercholesterolemia
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2000 (estimated)
- Study startJul 1987
- Study completionJun 1992
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (20)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular DiseasesStudies of the same condition, open and under way.
- More trials run by University of WashingtonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Investigators
- Melissa Austin, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00005203
- Sponsor's protocol ID
- 1082
- Other IDs
- R29HL038760
- Status last verified
- Aug 2004
- First submitted
- 25 May 2000
- Last updated
- 10 Feb 2016
- Results posted
- No
Publications
Austin MA. Genetic epidemiology of low-density lipoprotein subclass phenotypes. Ann Med. 1992 Dec;24(6):477-81. doi: 10.3109/07853899209166999.
PubMed 1485942Austin MA, Horowitz H, Wijsman E, Krauss RM, Brunzell J. Bimodality of plasma apolipoprotein B levels in familial combined hyperlipidemia. Atherosclerosis. 1992 Jan;92(1):67-77. doi: 10.1016/0021-9150(92)90011-5.
PubMed 1575822Austin MA. Low-density lipoprotein subclass phenotypes and familial combined hyperlipidemia. Diabetes Metab Rev. 1991 Sep;7(3):173-7. doi: 10.1002/dmr.5610070306. No abstract available.
PubMed 1817002Austin MA, Wijsman E, Guo SW, Krauss RM, Brunzell JD, Deeb S. Lack of evidence for linkage between low-density lipoprotein subclass phenotypes and the apolipoprotein B locus in familial combined hyperlipidemia. Genet Epidemiol. 1991;8(5):287-97. doi: 10.1002/gepi.1370080502.
PubMed 1761202LaBelle M, Austin MA, Rubin E, Krauss RM. Linkage analysis of low-density lipoprotein subclass phenotypes and the apolipoprotein B gene. Genet Epidemiol. 1991;8(4):269-75. doi: 10.1002/gepi.1370080407.
PubMed 1756949Austin MA. Plasma triglyceride and coronary heart disease. Arterioscler Thromb. 1991 Jan-Feb;11(1):2-14. doi: 10.1161/01.atv.11.1.2.
PubMed 1987999Brunzell JD, Austin MA. Individuality, hyperlipidemia, and premature coronary artery disease. World Rev Nutr Diet. 1990;63:72-83. doi: 10.1159/000418499. No abstract available.
PubMed 2197808Austin MA, King MC, Vranizan KM, Krauss RM. Atherogenic lipoprotein phenotype. A proposed genetic marker for coronary heart disease risk. Circulation. 1990 Aug;82(2):495-506. doi: 10.1161/01.cir.82.2.495.
PubMed 2372896Austin MA, Brunzell JD, Fitch WL, Krauss RM. Inheritance of low density lipoprotein subclass patterns in familial combined hyperlipidemia. Arteriosclerosis. 1990 Jul-Aug;10(4):520-30. doi: 10.1161/01.atv.10.4.520.
PubMed 2369363Austin MA, Sandholzer C, Selby JV, Newman B, Krauss RM, Utermann G. Lipoprotein(a) in women twins: heritability and relationship to apolipoprotein(a) phenotypes. Am J Hum Genet. 1992 Oct;51(4):829-40.
PubMed 1415225Selby JV, Austin MA, Sandholzer C, Quesenberry CP Jr, Zhang D, Mayer E, Utermann G. Environmental and behavioral influences on plasma lipoprotein(a) concentration in women twins. Prev Med. 1994 May;23(3):345-53. doi: 10.1006/pmed.1994.1048.
PubMed 8078856Austin 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.
PubMed 8314067Cheung MC, Austin MA, Moulin P, Wolf AC, Cryer D, Knopp RH. Effects of pravastatin on apolipoprotein-specific high density lipoprotein subpopulations and low density lipoprotein subclass phenotypes in patients with primary hypercholesterolemia. Atherosclerosis. 1993 Aug;102(1):107-19. doi: 10.1016/0021-9150(93)90089-d.
PubMed 8257447Selby JV, Austin MA, Newman B, Zhang D, Quesenberry CP Jr, Mayer EJ, Krauss RM. LDL subclass phenotypes and the insulin resistance syndrome in women. Circulation. 1993 Aug;88(2):381-7. doi: 10.1161/01.cir.88.2.381.
PubMed 8339401Austin MA, Newman B, Selby JV, Edwards K, Mayer EJ, Krauss RM. Genetics of LDL subclass phenotypes in women twins. Concordance, heritability, and commingling analysis. Arterioscler Thromb. 1993 May;13(5):687-95. doi: 10.1161/01.atv.13.5.687.
PubMed 8485120
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetics of Low Density Lipoprotein Subclasses in Hypercholesterolemia
- ClinicalTrials.gov ID
- NCT00005203
- Acronym / sponsor ID
- 1082
- Study type
- Observational
- Recruitment status
- Completed
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Jul 1987
- Study completion
- Jun 1992
- First posted
- 26 May 2000 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To perform genetic studies of low density lipoprotein (LDL) subclasses in 160 families in whom the probands had metabolically defined hypercholesterolemia.
Detailed description
BACKGROUND:
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.
DESIGN NARRATIVE:
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 design
Who may qualify
- Ages
- Up to 100 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2016.
- Background: PubMed 1485942Austin MA. Genetic epidemiology of low-density lipoprotein subclass phenotypes. Ann Med. 1992 Dec;24(6):477-81. doi: 10.3109/07853899209166999.
- Background: PubMed 1575822Austin MA, Horowitz H, Wijsman E, Krauss RM, Brunzell J. Bimodality of plasma apolipoprotein B levels in familial combined hyperlipidemia. Atherosclerosis. 1992 Jan;92(1):67-77. doi: 10.1016/0021-9150(92)90011-5.
- Background: PubMed 1817002Austin MA. Low-density lipoprotein subclass phenotypes and familial combined hyperlipidemia. Diabetes Metab Rev. 1991 Sep;7(3):173-7. doi: 10.1002/dmr.5610070306. No abstract available.
- Background: PubMed 1761202Austin MA, Wijsman E, Guo SW, Krauss RM, Brunzell JD, Deeb S. Lack of evidence for linkage between low-density lipoprotein subclass phenotypes and the apolipoprotein B locus in familial combined hyperlipidemia. Genet Epidemiol. 1991;8(5):287-97. doi: 10.1002/gepi.1370080502.
- Background: PubMed 1756949LaBelle M, Austin MA, Rubin E, Krauss RM. Linkage analysis of low-density lipoprotein subclass phenotypes and the apolipoprotein B gene. Genet Epidemiol. 1991;8(4):269-75. doi: 10.1002/gepi.1370080407.
- Background: PubMed 1987999Austin MA. Plasma triglyceride and coronary heart disease. Arterioscler Thromb. 1991 Jan-Feb;11(1):2-14. doi: 10.1161/01.atv.11.1.2.
- Background: PubMed 2197808Brunzell JD, Austin MA. Individuality, hyperlipidemia, and premature coronary artery disease. World Rev Nutr Diet. 1990;63:72-83. doi: 10.1159/000418499. No abstract available.
- Background: PubMed 2372896Austin MA, King MC, Vranizan KM, Krauss RM. Atherogenic lipoprotein phenotype. A proposed genetic marker for coronary heart disease risk. Circulation. 1990 Aug;82(2):495-506. doi: 10.1161/01.cir.82.2.495.
- Background: PubMed 2369363Austin MA, Brunzell JD, Fitch WL, Krauss RM. Inheritance of low density lipoprotein subclass patterns in familial combined hyperlipidemia. Arteriosclerosis. 1990 Jul-Aug;10(4):520-30. doi: 10.1161/01.atv.10.4.520.
- Background: PubMed 1415225Austin MA, Sandholzer C, Selby JV, Newman B, Krauss RM, Utermann G. Lipoprotein(a) in women twins: heritability and relationship to apolipoprotein(a) phenotypes. Am J Hum Genet. 1992 Oct;51(4):829-40.
- Background: PubMed 8078856Selby JV, Austin MA, Sandholzer C, Quesenberry CP Jr, Zhang D, Mayer E, Utermann G. Environmental and behavioral influences on plasma lipoprotein(a) concentration in women twins. Prev Med. 1994 May;23(3):345-53. doi: 10.1006/pmed.1994.1048.
- Background: PubMed 8314067Austin 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Melissa Austin
University of Washington
Questions about this trial
What is this clinical trial studying?
An observational study of Cardiovascular Diseases and Heart Diseases, run by University of Washington.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00005203, which also lists 20 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2016.