Coronary ArteriosclerosisNCT00005183
Apolipoprotein A-I Gene Polymorphism and Atherosclerosis
An observational study of Coronary Arteriosclerosis and Cardiovascular Diseases, run by Tufts University.
Trial summary
To further define the linkage of the Apo A-I gene polymorphism to genetic high density lipoprotein (HDL) deficiency and premature coronary artery disease. Also, to utilize this gene marker to define the prevalence of genetic HDL deficiency in patients with premature coronary disease and to determine the relative risk… Read more about this study
- Who is it for?
- Ages Up to 100 years, men only
- Conditions the study is for
- Coronary Arteriosclerosis, Cardiovascular Diseases, Heart Diseases
- How many people
- Not given
- Where
- No sites listed yet
- Study dates
- Dec 1985to Nov 1988
- 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 further define the linkage of the Apo A-I gene polymorphism to genetic high density lipoprotein (HDL) deficiency and premature coronary artery disease. Also, to utilize this gene marker to define the prevalence of genetic HDL deficiency in patients with premature coronary disease and to determine the relative risk of premature coronary disease associated with the Apo A-I gene polymorphism.
Read the detailed description
BACKGROUND:
Apolipoprotein (apo) A-I is the major protein constituent of plasma high density lipoproteins (HDL). HDL has been shown to promote cholesterol efflux from cells in vitro. Decreased plasma concentrations of HDL cholesterol and Apo A-I have been associated with premature coronary artery disease due to atherosclerosis in our society. A genetic HDL deficiency, familial hypoalphalipoproteinemia, appears to be fairly common in patients with premature coronary artery disease. The gene for Apo A-I has been isolated and characterized. Preliminary studies indicate that a specific Apo A-I gene polymorphism, detected following Pst I restriction enzyme digestion utilizing a specific probe, is significantly more common in subjects with premature coronary artery disease than in normal control subjects, and in some kindreds is associated with genetic HDL deficiency. This Apo A-I gene polymorphism is due to an alteration in the Apo A-I, Apo C-III intergenic region, near the 3' end of the coding region for Apo A-I. These observations have important implications for the detection of individuals genetically predisposed to premature coronary disease, as well as for providing insights into the mechanism leading to atherosclerosis.
DESIGN NARRATIVE:
Questionnaires were used to obtain information from each patient on known risk factors and diet. Fasting blood samples were obtained for lipoprotein analysis. Standard clinical and cardiological information and fasting blood samples were also collected for the cases. Blood was drawn for the DNA studies. A determination was made as to whether the Pst I Apo A-I gene polymorphism was associated with diminished levels of plasma Apo A-I or HDL cholesterol, by analysis of the distribution of these variables in cases and controls, after controlling for other known risk factors. Linkage analysis was used to determine whether the Pst I Apo A-I gene polymorphism co-segregates with premature coronary disease, or with diminished levels of plasma Apo A-I, or HDL cholesterol in 50 kindreds. A characterization was made of the abnormality in the Apo A-I, Apo C-III, Apo A-IV gene complex in patients with HDL deficiency, premature coronary disease, and the Pst I Apo A-I gene polymorphism.
- Medical subject headings
- Coronary Artery Disease, Cardiovascular Diseases, Heart Diseases, Atherosclerosis
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 startDec 1985
- Study completionNov 1988
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (46)Papers the sponsor has linked to this study.
- Other trials for Coronary ArteriosclerosisStudies of the same condition, open and under way.
- 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
- Tufts University
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00005183
- Sponsor's protocol ID
- 1061
- Other IDs
- R01HL035243
- Status last verified
- Dec 2017
- First submitted
- 25 May 2000
- Last updated
- 21 Dec 2017
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Genest J Jr, Bard JM, Fruchart JC, Ordovas JM, Schaefer EJ. Familial hypoalphalipoproteinemia in premature coronary artery disease. Arterioscler Thromb. 1993 Dec;13(12):1728-37. doi: 10.1161/01.atv.13.12.1728.
PubMed 8241092Reisher SR, Hughes TE, Ordovas JM, Schaefer EJ, Feinstein SI. Increased expression of apolipoprotein genes accompanies differentiation in the intestinal cell line Caco-2. Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5757-61. doi: 10.1073/pnas.90.12.5757.
PubMed 8516325Jenner JL, Ordovas JM, Lamon-Fava S, Schaefer MM, Wilson PW, Castelli WP, Schaefer EJ. Effects of age, sex, and menopausal status on plasma lipoprotein(a) levels. The Framingham Offspring Study. Circulation. 1993 Apr;87(4):1135-41. doi: 10.1161/01.cir.87.4.1135.
PubMed 8462142Ordovas JM, Schaefer EJ, Salem D, Ward RH, Glueck CJ, Vergani C, Wilson PW, Karathanasis SK. Apolipoprotein A-I gene polymorphism associated with premature coronary artery disease and familial hypoalphalipoproteinemia. N Engl J Med. 1986 Mar 13;314(11):671-7. doi: 10.1056/NEJM198603133141102.
PubMed 3081805Schaefer EJ, McNamara JR, Mitri C, Ordovas JM: Genetic High Density Lipoprotein Deficiency States. Atherosclerosis VII. Proceedings of the Seventh International Symposium on Atherosclerosis, Excerpta Medica, Amsterdam, p 183-186, 1986
Schaefer EJ, McNamara JR, Mitri CJ, Ordovas JM. Genetic high density lipoprotein deficiency states and atherosclerosis. Adv Exp Med Biol. 1986;201:1-15. doi: 10.1007/978-1-4684-1262-8_1. No abstract available.
PubMed 3099550Haddad IA, Ordovas JM, Fitzpatrick T, Karathanasis SK. Linkage, evolution, and expression of the rat apolipoprotein A-I, C-III, and A-IV genes. J Biol Chem. 1986 Oct 5;261(28):13268-77.
PubMed 3020028Schaefer EJ, Gregg RE, Ghiselli G, Forte TM, Ordovas JM, Zech LA, Brewer HB Jr. Familial apolipoprotein E deficiency. J Clin Invest. 1986 Nov;78(5):1206-19. doi: 10.1172/JCI112704.
PubMed 3771793Lamon-Fava S, Ordovas JM, Mandel G, Forte TM, Goodman RH, Schaefer EJ. Secretion of apolipoprotein A-I in lipoprotein particles following transfection of the human apolipoprotein A-I gene into 3T3 cells. J Biol Chem. 1987 Jul 5;262(19):8944-7.
PubMed 3110151Hughes TE, Sasak WV, Ordovas JM, Forte TM, Lamon-Fava S, Schaefer EJ. A novel cell line (Caco-2) for the study of intestinal lipoprotein synthesis. J Biol Chem. 1987 Mar 15;262(8):3762-7.
PubMed 3818664Ordovas JM, Peterson JP, Santaniello P, Cohn JS, Wilson PW, Schaefer EJ. Enzyme-linked immunosorbent assay for human plasma apolipoprotein B. J Lipid Res. 1987 Oct;28(10):1216-24.
PubMed 3681146Ordovas JM, Litwack-Klein L, Wilson PW, Schaefer MM, Schaefer EJ. Apolipoprotein E isoform phenotyping methodology and population frequency with identification of apoE1 and apoE5 isoforms. J Lipid Res. 1987 Apr;28(4):371-80.
PubMed 3585172McNamara JR, Campos H, Ordovas JM, Peterson J, Wilson PW, Schaefer EJ. Effect of gender, age, and lipid status on low density lipoprotein subfraction distribution. Results from the Framingham Offspring Study. Arteriosclerosis. 1987 Sep-Oct;7(5):483-90. doi: 10.1161/01.atv.7.5.483.
PubMed 3675308Hughes TE, Ordovas JM, Schaefer EJ. Regulation of intestinal apolipoprotein B synthesis and secretion by Caco-2 cells. Lack of fatty acid effects and control by intracellular calcium ion. J Biol Chem. 1988 Mar 5;263(7):3425-31.
PubMed 3125180Schaefer EJ, McNamara JR, Genest J, Ordovas JM. Genetics and abnormalities in metabolism of lipoproteins. Clin Chem. 1988;34(8B):B9-12. No abstract available.
PubMed 3042205
Study at a glance
From the registry record, last updated by the sponsor on 21 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Apolipoprotein A-I Gene Polymorphism and Atherosclerosis
- ClinicalTrials.gov ID
- NCT00005183
- Acronym / sponsor ID
- 1061
- Study type
- Observational
- Recruitment status
- Completed
- Lead sponsor
- Tufts UniversityUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Dec 1985
- Study completion
- Nov 1988
- 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 further define the linkage of the Apo A-I gene polymorphism to genetic high density lipoprotein (HDL) deficiency and premature coronary artery disease. Also, to utilize this gene marker to define the prevalence of genetic HDL deficiency in patients with premature coronary disease and to determine the relative risk of premature coronary disease associated with the Apo A-I gene polymorphism.
Detailed description
BACKGROUND:
Apolipoprotein (apo) A-I is the major protein constituent of plasma high density lipoproteins (HDL). HDL has been shown to promote cholesterol efflux from cells in vitro. Decreased plasma concentrations of HDL cholesterol and Apo A-I have been associated with premature coronary artery disease due to atherosclerosis in our society. A genetic HDL deficiency, familial hypoalphalipoproteinemia, appears to be fairly common in patients with premature coronary artery disease. The gene for Apo A-I has been isolated and characterized. Preliminary studies indicate that a specific Apo A-I gene polymorphism, detected following Pst I restriction enzyme digestion utilizing a specific probe, is significantly more common in subjects with premature coronary artery disease than in normal control subjects, and in some kindreds is associated with genetic HDL deficiency. This Apo A-I gene polymorphism is due to an alteration in the Apo A-I, Apo C-III intergenic region, near the 3' end of the coding region for Apo A-I. These observations have important implications for the detection of individuals genetically predisposed to premature coronary disease, as well as for providing insights into the mechanism leading to atherosclerosis.
DESIGN NARRATIVE:
Questionnaires were used to obtain information from each patient on known risk factors and diet. Fasting blood samples were obtained for lipoprotein analysis. Standard clinical and cardiological information and fasting blood samples were also collected for the cases. Blood was drawn for the DNA studies. A determination was made as to whether the Pst I Apo A-I gene polymorphism was associated with diminished levels of plasma Apo A-I or HDL cholesterol, by analysis of the distribution of these variables in cases and controls, after controlling for other known risk factors. Linkage analysis was used to determine whether the Pst I Apo A-I gene polymorphism co-segregates with premature coronary disease, or with diminished levels of plasma Apo A-I, or HDL cholesterol in 50 kindreds. A characterization was made of the abnormality in the Apo A-I, Apo C-III, Apo A-IV gene complex in patients with HDL deficiency, premature coronary disease, and the Pst I Apo A-I gene polymorphism.
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 21 Dec 2017.
- Background: PubMed 8241092Genest J Jr, Bard JM, Fruchart JC, Ordovas JM, Schaefer EJ. Familial hypoalphalipoproteinemia in premature coronary artery disease. Arterioscler Thromb. 1993 Dec;13(12):1728-37. doi: 10.1161/01.atv.13.12.1728.
- Background: PubMed 8516325Reisher SR, Hughes TE, Ordovas JM, Schaefer EJ, Feinstein SI. Increased expression of apolipoprotein genes accompanies differentiation in the intestinal cell line Caco-2. Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5757-61. doi: 10.1073/pnas.90.12.5757.
- Background: PubMed 8462142Jenner JL, Ordovas JM, Lamon-Fava S, Schaefer MM, Wilson PW, Castelli WP, Schaefer EJ. Effects of age, sex, and menopausal status on plasma lipoprotein(a) levels. The Framingham Offspring Study. Circulation. 1993 Apr;87(4):1135-41. doi: 10.1161/01.cir.87.4.1135.
- Background: PubMed 3081805Ordovas JM, Schaefer EJ, Salem D, Ward RH, Glueck CJ, Vergani C, Wilson PW, Karathanasis SK. Apolipoprotein A-I gene polymorphism associated with premature coronary artery disease and familial hypoalphalipoproteinemia. N Engl J Med. 1986 Mar 13;314(11):671-7. doi: 10.1056/NEJM198603133141102.
- BackgroundSchaefer EJ, McNamara JR, Mitri C, Ordovas JM: Genetic High Density Lipoprotein Deficiency States. Atherosclerosis VII. Proceedings of the Seventh International Symposium on Atherosclerosis, Excerpta Medica, Amsterdam, p 183-186, 1986
- Background: PubMed 3099550Schaefer EJ, McNamara JR, Mitri CJ, Ordovas JM. Genetic high density lipoprotein deficiency states and atherosclerosis. Adv Exp Med Biol. 1986;201:1-15. doi: 10.1007/978-1-4684-1262-8_1. No abstract available.
- Background: PubMed 3020028Haddad IA, Ordovas JM, Fitzpatrick T, Karathanasis SK. Linkage, evolution, and expression of the rat apolipoprotein A-I, C-III, and A-IV genes. J Biol Chem. 1986 Oct 5;261(28):13268-77.
- Background: PubMed 3771793Schaefer EJ, Gregg RE, Ghiselli G, Forte TM, Ordovas JM, Zech LA, Brewer HB Jr. Familial apolipoprotein E deficiency. J Clin Invest. 1986 Nov;78(5):1206-19. doi: 10.1172/JCI112704.
- Background: PubMed 3110151Lamon-Fava S, Ordovas JM, Mandel G, Forte TM, Goodman RH, Schaefer EJ. Secretion of apolipoprotein A-I in lipoprotein particles following transfection of the human apolipoprotein A-I gene into 3T3 cells. J Biol Chem. 1987 Jul 5;262(19):8944-7.
- Background: PubMed 3818664Hughes TE, Sasak WV, Ordovas JM, Forte TM, Lamon-Fava S, Schaefer EJ. A novel cell line (Caco-2) for the study of intestinal lipoprotein synthesis. J Biol Chem. 1987 Mar 15;262(8):3762-7.
- Background: PubMed 3681146Ordovas JM, Peterson JP, Santaniello P, Cohn JS, Wilson PW, Schaefer EJ. Enzyme-linked immunosorbent assay for human plasma apolipoprotein B. J Lipid Res. 1987 Oct;28(10):1216-24.
- Background: PubMed 3585172Ordovas JM, Litwack-Klein L, Wilson PW, Schaefer MM, Schaefer EJ. Apolipoprotein E isoform phenotyping methodology and population frequency with identification of apoE1 and apoE5 isoforms. J Lipid Res. 1987 Apr;28(4):371-80.
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
An observational study of Coronary Arteriosclerosis and Cardiovascular Diseases, run by Tufts University.
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 21 Dec 2017. 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 NCT00005183, which also lists 46 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 21 Dec 2017.