Cardiovascular DiseasesNCT00005335
Genetic Epidemiology of Lipoprotein-Lipid Levels
An observational study of Cardiovascular Diseases and Heart Diseases, run by National Heart, Lung, and Blood Institute (NHLBI).
Trial summary
To determine the contribution of polymorphic variation in candidate genes involved in lipid metabolism in determining quantitative lipoprotein-lipid levels and cardiovascular risk factors in Anglo and Hispanic populations of the San Luis Valley in southern Colorado. Read more about this study
- Who is it for?
- Ages Up to 100 years
- Conditions the study is for
- Cardiovascular Diseases, Heart Diseases, Atherosclerosis
- How many people
- Not given
- Where
- No sites listed yet
- Study dates
- May 1991to Mar 2002
- 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
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
No eligibility criteria
About this study
To determine the contribution of polymorphic variation in candidate genes involved in lipid metabolism in determining quantitative lipoprotein-lipid levels and cardiovascular risk factors in Anglo and Hispanic populations of the San Luis Valley in southern Colorado. The candidate genes included those for A-IV, B, D, E, H, APO(a), LDL receptor, hepatic lipase, lipoprotein lipase, lethicin cholesterol acyletransferase (LCAT), and cholesteryl ester transfer protein.
Read the detailed description
DESIGN NARRATIVE:
Beginning in 1991, genetic variations in the gene products of A-IV, E, H, and APO(a) were determined by isoelectric focusing and SDS/immunoblotting; gene variations at the APOB, D, LDL receptor, hepatic lipase, lipoprotein lipase, and cholesteryl ester transfer protein were assayed by polymerase chain reaction protocols and by using cloned cDNA probes for restriction fragment length polymorphism (RFLP) analyses. Direct haplotype analyses of individuals employed a strategy using RFLP analysis combined with the use of allele specific oligonucleotides. Quantitative levels of apolipoprotein B, E, H and APO (a) were determined by immunological techniques. These data and prior data on levels of triglycerides, total cholesterol, HDL-, LDL- and HDL subfraction cholesterol were used in the quantitative genetic analysis. Estimates of the effect of alleles at each of the genetic loci on the quantitative apolipoprotein and lipoprotein levels employed the measured genotype approach. The effects of multisite haplotypes for RFLPs at various loci were estimated using the same methods. For common alleles in each system, estimates were made of the interaction of alleles at independent genetic loci in determining quantitative variables. Dietary information from the San Luis Valley population was used to estimate cholesterol intake identified. Allelic effects were estimated in these groups to gain insight into the effect of dietary cholesterol intake of the estimated allelic effects.
The study was renewed in fiscal year 1996 to determine the contribution of polymorphic variation in nine candidate genes involved in lipid metabolism [APO(a), APOD, hepatic lipase (HL), cholesteryl ester transfer protein (CETP), LDL receptor related protein (LRP), 3- hydroxy-3 methyl glutryl-coenzyme A (HMG COA), VLDL-receptor, Lecithin cholesterol acyletransferase (LCAT) and paraoxonase (PON)] in determining quantitative lipoprotein-lipid levels in Hispanics and non-Hispanic Whites of the San Luis Valley, Colorado. The study also determined the molecular basis of the functional mutation in the lipoprotein lipase (LPL) gene which is associated with plasma triglyceride and HDL cholesterol variations. The objectives were achieved by fulfilling the following specific aims: 1) by PCR, DNA sequencing and SSCP analyses, all coding exons and putative regulatory elements in the LPL gene of individuals who were homozygous for the HindIII restriction site to detect nucleotide changes in the coding region which affected directly triglycerides and HDL-cholesterol levels werescreened, in vitro mutagenesis and expression studies were conducted to confirm which of the putative functional mutations was the actual functional mutation; 2) genetic variations in genes coding for CETP, HL, LRP, APOD, HMG COA, VLDL-receptor, LCAT and PON were identified by PCR or standard Southern blotting techniques, and the impact of individual polymorphisms and the joint impact of polymorphisms at different loci (genotype-genotype interaction) in determining quantitative lipoprotein-lipid levels in Hispanics and non-Hispanic whites were estimated; and 3) the distribution of APO(a) kringle 4 and pentanucleotide polymorphisms were determined by SDS-agarose gel electrophoresis and PCR, respectively, and LP(a) levels were quantified by enzyme-linked immunosorbent assay, and the correlation between APO(a) polymorphisms and LP(a) levels were investigated.
The study completion date listed in this record was obtained from the "End Date" entered in the Protocol Registration and Results System (PRS) record.
- Conditions
- Cardiovascular Diseases, Heart Diseases, Atherosclerosis
- Medical subject headings
- 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 startMay 1991
- Study completionMar 2002
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (26)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 National Heart, Lung, and Blood Institute (NHLBI)The 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
- Sponsor type
- US National Institutes of Health
- Investigators
- Mohammad Kamboh, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00005335
- Sponsor's protocol ID
- 4192
- Other IDs
- R01HL044672
- Status last verified
- Jul 2004
- First submitted
- 25 May 2000
- Last updated
- 13 May 2016
- Results posted
- No
Publications
Kamboh MI, Kelly LJ, Ahn YI, Ferrell RE. Genetic polymorphism of apolipoprotein A-IV in the chimpanzee: common deletion of a conserved 12-nucleotide tandem repeat. Hum Biol. 1994 Aug;66(4):625-38.
PubMed 8088751Rewers M, Kamboh MI, Hoag S, Shetterly SM, Ferrell RE, Hamman RF. ApoA-IV polymorphism associated with myocardial infarction in obese NIDDM patients. The San Luis Valley Diabetes Study. Diabetes. 1994 Dec;43(12):1485-9. doi: 10.2337/diab.43.12.1485.
PubMed 7958503Kamboh MI, Svitko CM, Williams ER, Ferrell RE, Pollitzer WS. Hypervariable polymorphism of APO(a) in blacks and whites as reflected by phenotyping. Chem Phys Lipids. 1994 Jan;67-68:283-92. doi: 10.1016/0009-3084(94)90148-1.
PubMed 8187225Ahn YI, Kamboh MI, Aston CE, Ferrell RE, Hamman RF. Role of common genetic polymorphisms in the LDL receptor gene in affecting plasma cholesterol levels in the general population. Arterioscler Thromb. 1994 May;14(5):663-70. doi: 10.1161/01.atv.14.5.663.
PubMed 8172843Kamboh MI, Friedlaender JS, Ahn YI, Ferrell RE. A common deletion polymorphism in the apolipoprotein A4 gene and its significance in lipid metabolism. Arterioscler Thromb. 1994 May;14(5):656-62. doi: 10.1161/01.atv.14.5.656.
PubMed 8172842Ahn YI, Ferrell RE, Hamman RF, Kamboh MI. Association of lipoprotein lipase gene variation with the physiological components of the insulin-resistance syndrome in the population of the San Luis Valley, Colorado. Diabetes Care. 1993 Nov;16(11):1502-6. doi: 10.2337/diacare.16.11.1502.
PubMed 7905375Cole SA, Aston CE, Hamman RF, Ferrell RE. Association of a PvuII RFLP at the lipoprotein lipase locus with fasting insulin levels in Hispanic men. Genet Epidemiol. 1993;10(3):177-88. doi: 10.1002/gepi.1370100304.
PubMed 8102341Ahn YI, Kamboh MI, Hamman RF, Cole SA, Ferrell RE. Two DNA polymorphisms in the lipoprotein lipase gene and their associations with factors related to cardiovascular disease. J Lipid Res. 1993 Mar;34(3):421-8.
PubMed 8096867Saha N, Kamboh MI, Ahn YA, Tay JS, Ferrell RE. Apolipoprotein H polymorphism and serum lipoprotein and apolipoprotein levels in two Asian populations. Ethn Dis. 1993 Summer;3(3):250-4.
PubMed 8167541Crews DE, Kamboh MI, Mancilha-Carvalho JJ, Kottke B. Population genetics of apolipoprotein A-4, E, and H polymorphisms in Yanomami Indians of northwestern Brazil: associations with lipids, lipoproteins, and carbohydrate metabolism. Hum Biol. 1993 Apr;65(2):211-24.
PubMed 8449482Sanghera DK, Aston CE, Saha N, Kamboh MI. DNA polymorphisms in two paraoxonase genes (PON1 and PON2) are associated with the risk of coronary heart disease. Am J Hum Genet. 1998 Jan;62(1):36-44. doi: 10.1086/301669.
PubMed 9443862Kamboh MI, Rewers M, Aston CE, Hamman RF. Plasma apolipoprotein A-I, apolipoprotein B, and lipoprotein(a) concentrations in normoglycemic Hispanics and non-Hispanic whites from the San Luis Valley, Colorado. Am J Epidemiol. 1997 Dec 15;146(12):1011-8. doi: 10.1093/oxfordjournals.aje.a009229.
PubMed 9420525Saha N, Wang G, Vasisht S, Kamboh MI. Influence of two apo A4 polymorphisms at codons 347 and 360 on non-fasting plasma lipoprotein-lipids and apolipoproteins in Asian Indians. Atherosclerosis. 1997 Jun;131(2):249-55. doi: 10.1016/s0021-9150(97)06112-1.
PubMed 9199279Sanghera DK, Saha N, Aston CE, Kamboh MI. Genetic polymorphism of paraoxonase and the risk of coronary heart disease. Arterioscler Thromb Vasc Biol. 1997 Jun;17(6):1067-73. doi: 10.1161/01.atv.17.6.1067.
PubMed 9194756Kamboh MI, Aston CE, Nestlerode CM, McAllister AE, Hamman RF. Haplotype analysis of two APOA1/MspI polymorphisms in relation to plasma levels of apo A-I and HDL-cholesterol. Atherosclerosis. 1996 Dec 20;127(2):255-62. doi: 10.1016/s0021-9150(96)05966-7.
PubMed 9125316
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetic Epidemiology of Lipoprotein-Lipid Levels
- ClinicalTrials.gov ID
- NCT00005335
- Acronym / sponsor ID
- 4192
- Conditions
- Cardiovascular Diseases, Heart Diseases, Atherosclerosis
- Study type
- Observational
- Recruitment status
- Completed
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- May 1991
- Study completion
- Mar 2002 (actual)
- 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 determine the contribution of polymorphic variation in candidate genes involved in lipid metabolism in determining quantitative lipoprotein-lipid levels and cardiovascular risk factors in Anglo and Hispanic populations of the San Luis Valley in southern Colorado. The candidate genes included those for A-IV, B, D, E, H, APO(a), LDL receptor, hepatic lipase, lipoprotein lipase, lethicin cholesterol acyletransferase (LCAT), and cholesteryl ester transfer protein.
Detailed description
DESIGN NARRATIVE:
Beginning in 1991, genetic variations in the gene products of A-IV, E, H, and APO(a) were determined by isoelectric focusing and SDS/immunoblotting; gene variations at the APOB, D, LDL receptor, hepatic lipase, lipoprotein lipase, and cholesteryl ester transfer protein were assayed by polymerase chain reaction protocols and by using cloned cDNA probes for restriction fragment length polymorphism (RFLP) analyses. Direct haplotype analyses of individuals employed a strategy using RFLP analysis combined with the use of allele specific oligonucleotides. Quantitative levels of apolipoprotein B, E, H and APO (a) were determined by immunological techniques. These data and prior data on levels of triglycerides, total cholesterol, HDL-, LDL- and HDL subfraction cholesterol were used in the quantitative genetic analysis. Estimates of the effect of alleles at each of the genetic loci on the quantitative apolipoprotein and lipoprotein levels employed the measured genotype approach. The effects of multisite haplotypes for RFLPs at various loci were estimated using the same methods. For common alleles in each system, estimates were made of the interaction of alleles at independent genetic loci in determining quantitative variables. Dietary information from the San Luis Valley population was used to estimate cholesterol intake identified. Allelic effects were estimated in these groups to gain insight into the effect of dietary cholesterol intake of the estimated allelic effects.
The study was renewed in fiscal year 1996 to determine the contribution of polymorphic variation in nine candidate genes involved in lipid metabolism [APO(a), APOD, hepatic lipase (HL), cholesteryl ester transfer protein (CETP), LDL receptor related protein (LRP), 3- hydroxy-3 methyl glutryl-coenzyme A (HMG COA), VLDL-receptor, Lecithin cholesterol acyletransferase (LCAT) and paraoxonase (PON)] in determining quantitative lipoprotein-lipid levels in Hispanics and non-Hispanic Whites of the San Luis Valley, Colorado. The study also determined the molecular basis of the functional mutation in the lipoprotein lipase (LPL) gene which is associated with plasma triglyceride and HDL cholesterol variations. The objectives were achieved by fulfilling the following specific aims: 1) by PCR, DNA sequencing and SSCP analyses, all coding exons and putative regulatory elements in the LPL gene of individuals who were homozygous for the HindIII restriction site to detect nucleotide changes in the coding region which affected directly triglycerides and HDL-cholesterol levels werescreened, in vitro mutagenesis and expression studies were conducted to confirm which of the putative functional mutations was the actual functional mutation; 2) genetic variations in genes coding for CETP, HL, LRP, APOD, HMG COA, VLDL-receptor, LCAT and PON were identified by PCR or standard Southern blotting techniques, and the impact of individual polymorphisms and the joint impact of polymorphisms at different loci (genotype-genotype interaction) in determining quantitative lipoprotein-lipid levels in Hispanics and non-Hispanic whites were estimated; and 3) the distribution of APO(a) kringle 4 and pentanucleotide polymorphisms were determined by SDS-agarose gel electrophoresis and PCR, respectively, and LP(a) levels were quantified by enzyme-linked immunosorbent assay, and the correlation between APO(a) polymorphisms and LP(a) levels were investigated.
The study completion date listed in this record was obtained from the "End Date" entered in the Protocol Registration and Results System (PRS) record.
Study design
Who may qualify
- Ages
- Up to 100 years
- Sex
- All
- 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 13 May 2016.
- Background: PubMed 8088751Kamboh MI, Kelly LJ, Ahn YI, Ferrell RE. Genetic polymorphism of apolipoprotein A-IV in the chimpanzee: common deletion of a conserved 12-nucleotide tandem repeat. Hum Biol. 1994 Aug;66(4):625-38.
- Background: PubMed 7958503Rewers M, Kamboh MI, Hoag S, Shetterly SM, Ferrell RE, Hamman RF. ApoA-IV polymorphism associated with myocardial infarction in obese NIDDM patients. The San Luis Valley Diabetes Study. Diabetes. 1994 Dec;43(12):1485-9. doi: 10.2337/diab.43.12.1485.
- Background: PubMed 8187225Kamboh MI, Svitko CM, Williams ER, Ferrell RE, Pollitzer WS. Hypervariable polymorphism of APO(a) in blacks and whites as reflected by phenotyping. Chem Phys Lipids. 1994 Jan;67-68:283-92. doi: 10.1016/0009-3084(94)90148-1.
- Background: PubMed 8172843Ahn YI, Kamboh MI, Aston CE, Ferrell RE, Hamman RF. Role of common genetic polymorphisms in the LDL receptor gene in affecting plasma cholesterol levels in the general population. Arterioscler Thromb. 1994 May;14(5):663-70. doi: 10.1161/01.atv.14.5.663.
- Background: PubMed 8172842Kamboh MI, Friedlaender JS, Ahn YI, Ferrell RE. A common deletion polymorphism in the apolipoprotein A4 gene and its significance in lipid metabolism. Arterioscler Thromb. 1994 May;14(5):656-62. doi: 10.1161/01.atv.14.5.656.
- Background: PubMed 7905375Ahn YI, Ferrell RE, Hamman RF, Kamboh MI. Association of lipoprotein lipase gene variation with the physiological components of the insulin-resistance syndrome in the population of the San Luis Valley, Colorado. Diabetes Care. 1993 Nov;16(11):1502-6. doi: 10.2337/diacare.16.11.1502.
- Background: PubMed 8102341Cole SA, Aston CE, Hamman RF, Ferrell RE. Association of a PvuII RFLP at the lipoprotein lipase locus with fasting insulin levels in Hispanic men. Genet Epidemiol. 1993;10(3):177-88. doi: 10.1002/gepi.1370100304.
- Background: PubMed 8096867Ahn YI, Kamboh MI, Hamman RF, Cole SA, Ferrell RE. Two DNA polymorphisms in the lipoprotein lipase gene and their associations with factors related to cardiovascular disease. J Lipid Res. 1993 Mar;34(3):421-8.
- Background: PubMed 8167541Saha N, Kamboh MI, Ahn YA, Tay JS, Ferrell RE. Apolipoprotein H polymorphism and serum lipoprotein and apolipoprotein levels in two Asian populations. Ethn Dis. 1993 Summer;3(3):250-4.
- Background: PubMed 8449482Crews DE, Kamboh MI, Mancilha-Carvalho JJ, Kottke B. Population genetics of apolipoprotein A-4, E, and H polymorphisms in Yanomami Indians of northwestern Brazil: associations with lipids, lipoproteins, and carbohydrate metabolism. Hum Biol. 1993 Apr;65(2):211-24.
- Background: PubMed 9443862Sanghera DK, Aston CE, Saha N, Kamboh MI. DNA polymorphisms in two paraoxonase genes (PON1 and PON2) are associated with the risk of coronary heart disease. Am J Hum Genet. 1998 Jan;62(1):36-44. doi: 10.1086/301669.
- Background: PubMed 9420525Kamboh MI, Rewers M, Aston CE, Hamman RF. Plasma apolipoprotein A-I, apolipoprotein B, and lipoprotein(a) concentrations in normoglycemic Hispanics and non-Hispanic whites from the San Luis Valley, Colorado. Am J Epidemiol. 1997 Dec 15;146(12):1011-8. doi: 10.1093/oxfordjournals.aje.a009229.
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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.
Mohammad Kamboh
University of Pittsburgh
Questions about this trial
What is this clinical trial studying?
An observational study of Cardiovascular Diseases and Heart Diseases, run by National Heart, Lung, and Blood Institute (NHLBI).
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 13 May 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 NCT00005335, which also lists 26 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 13 May 2016.