Cardiovascular DiseasesNCT00005490
Modeling DNA Diversity in Cardiovascular Health/Disease
An observational study of Cardiovascular Diseases and Heart Diseases, run by National Heart, Lung, and Blood Institute (NHLBI).
Trial summary
To identify and measure DNA sequence variation in 13 genes that play a central role in key physiological functions involved in the development of cardiovascular disease, that is, genes involved in lipid metabolism, carbohydrate metabolism, and blood pressure regulation. Read more about this study
- Who is it for?
- Ages Up to 100 years
- Conditions the study is for
- Cardiovascular Diseases, Heart Diseases
- How many people
- Not given
- Where
- No sites listed yet
- Study dates
- Aug 1997to Jun 2003
- 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 identify and measure DNA sequence variation in 13 genes that play a central role in key physiological functions involved in the development of cardiovascular disease, that is, genes involved in lipid metabolism, carbohydrate metabolism, and blood pressure regulation.
Read the detailed description
BACKGROUND:
One of the most complex and challenging problems in human biology and medicine is defining the relationship between DNA sequence variation and interindividual variation in quantitative risk factors for complex diseases having a multifactorial etiology. As the knowledge about the basic human DNA sequence increases, so will the need to define the range of natural variation in human populations and to explore the relationship between nucleotide diversity and phenotype variation in measures of human health.
DESIGN NARRATIVE:
The study was a collaborative one involving Dr. Deborah Nickerson at the University of Washington, Dr. Kenneth Weiss at Pennsylvania State University, and Dr. Charles Sing of the University of Michigan. Dr. Nickerson identified and measured DNA sequence variation in 13 genes that play a central role in key physiological functions involved in the development of cardiovascular disease. She applied state-of-the-art automated fluorescence-based sequencing and high-throughput DNA genotyping methods to uncover and assess DNA sequence variation in three human populations: non-Hispanic Whites from Rochester, MN (lowCVD risk), African-Americans from Jackson, MS (intermediate CVD risk) and non-Hispanic Whites from North Karelia,Finland (high CVD risk).
Dr. Weiss used the theoretical and statistical approaches of molecular population genetics to characterize the cumulative effects of population history on the amount, distribution, and structure of extant variation in 13 candidate CVD susceptibility genes in three populations. His tests of linkage equilibrium and of homogeneity of the variation across several levels of stratification (among individuals, demographic variables, parts of genes, populations, and among genes) further sharpened the understanding of the nature of human genetic variation, particularly with respect to candidate CVD susceptibility genes. He made inferences about functional constraints from gene trees and from patterns of divergence among human populations and between humans and the chimpanzee. Dr. Weiss's project provided the inferential engine that drove the sampling design and sample selection in Dr. Nickerson's project and provided the demographic/historical background necessary for genotype-phenotype inferences of Dr. Sing's project.
Dr. Sing developed models for the relationships between the DNA sequence variation in the 13 candidate CVD susceptibility genes identified, measured, and characterized in Dr. Nickerson's and Dr. Weiss's projects and variation in established quantitative risk factors for CVD, including total plasma cholesterol, HDL cholesterol, and triglycerides, and systolic and diastolic blood pressure collected from the 1,500 individuals. His project established which subset of DNA sequence variations in which candidate genes were associated with variation in CVD risk factors in which subset of individuals and in which of three populations. His elucidation of the relationships between DNA sequence variations and variations in intermediate biological risk factor traits revealed opportunities for intervention to alter the risk of CVD and establish whether such efforts should be directed across populations, within a population, or at an individual.
The study completion date listed in this record was obtained from the "End Date" entered in the old format Protocol Registration and Results System (PRS).
- Conditions
- Cardiovascular Diseases, Heart Diseases
- Medical subject headings
- Cardiovascular Diseases, Heart Diseases
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 startAug 1997
- Study completionJun 2003
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)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
- Deborah Nickerson, University of WashingtonCharles Sing, University of MichiganKenneth Weiss, Penn State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00005490
- Sponsor's protocol ID
- 5007
- Other IDs
- R01HL058238, R01HL058239, R01HL058240
- Status last verified
- Feb 2005
- First submitted
- 25 May 2000
- Last updated
- 7 Nov 2016
- Results posted
- No
Publications
Templeton AR, Clark AG, Weiss KM, Nickerson DA, Boerwinkle E, Sing CF. Recombinational and mutational hotspots within the human lipoprotein lipase gene. Am J Hum Genet. 2000 Jan;66(1):69-83. doi: 10.1086/302699.
PubMed 10631137Rieder MJ, Taylor SL, Clark AG, Nickerson DA. Sequence variation in the human angiotensin converting enzyme. Nat Genet. 1999 May;22(1):59-62. doi: 10.1038/8760.
PubMed 10319862Nickerson DA, Taylor SL, Weiss KM, Clark AG, Hutchinson RG, Stengard J, Salomaa V, Vartiainen E, Boerwinkle E, Sing CF. DNA sequence diversity in a 9.7-kb region of the human lipoprotein lipase gene. Nat Genet. 1998 Jul;19(3):233-40. doi: 10.1038/907.
PubMed 9662394Nelson MR, Kardia SL, Ferrell RE, Sing CF. Influence of apolipoprotein E genotype variation on the means, variances, and correlations of plasma lipids and apolipoproteins in children. Ann Hum Genet. 1999 Jul;63(Pt 4):311-28. doi: 10.1046/j.1469-1809.1999.6340311.x.
PubMed 10738543Stengard JH, Kardia SL, Tervahauta M, Ehnholm C, Nissinen A, Sing CF. Utility of the predictors of coronary heart disease mortality in a longitudinal study of elderly Finnish men aged 65 to 84 years is dependent on context defined by Apo E genotype and area of residence. Clin Genet. 1999 Nov;56(5):367-77. doi: 10.1034/j.1399-0004.1999.560505.x.
PubMed 10668927Kardia SL, Haviland MB, Ferrell RE, Sing CF. The relationship between risk factor levels and presence of coronary artery calcification is dependent on apolipoprotein E genotype. Arterioscler Thromb Vasc Biol. 1999 Feb;19(2):427-35. doi: 10.1161/01.atv.19.2.427.
PubMed 9974428Stengard JH, Weiss KM, Sing CF. An ecological study of association between coronary heart disease mortality rates in men and the relative frequencies of common allelic variations in the gene coding for apolipoprotein E. Hum Genet. 1998 Aug;103(2):234-41. doi: 10.1007/s004390050811.
PubMed 9760210Nickerson DA, Taylor SL, Fullerton SM, Weiss KM, Clark AG, Stengard JH, Salomaa V, Boerwinkle E, Sing CF. Sequence diversity and large-scale typing of SNPs in the human apolipoprotein E gene. Genome Res. 2000 Oct;10(10):1532-45. doi: 10.1101/gr.146900.
PubMed 11042151Fullerton SM, Clark AG, Weiss KM, Nickerson DA, Taylor SL, Stengard JH, Salomaa V, Vartiainen E, Perola M, Boerwinkle E, Sing CF. Apolipoprotein E variation at the sequence haplotype level: implications for the origin and maintenance of a major human polymorphism. Am J Hum Genet. 2000 Oct;67(4):881-900. doi: 10.1086/303070. Epub 2000 Sep 13.
PubMed 10986041Templeton AR, Weiss KM, Nickerson DA, Boerwinkle E, Sing CF. Cladistic structure within the human Lipoprotein lipase gene and its implications for phenotypic association studies. Genetics. 2000 Nov;156(3):1259-75. doi: 10.1093/genetics/156.3.1259.
PubMed 11063700Stengard JH, Clark AG, Weiss KM, Kardia S, Nickerson DA, Salomaa V, Ehnholm C, Boerwinkle E, Sing CF. Contributions of 18 additional DNA sequence variations in the gene encoding apolipoprotein E to explaining variation in quantitative measures of lipid metabolism. Am J Hum Genet. 2002 Sep;71(3):501-17. doi: 10.1086/342217. Epub 2002 Aug 5.
PubMed 12165926Fullerton SM, Clark AG, Weiss KM, Taylor SL, Stengard JH, Salomaa V, Boerwinkle E, Nickerson DA. Sequence polymorphism at the human apolipoprotein AII gene ( APOA2): unexpected deficit of variation in an African-American sample. Hum Genet. 2002 Jul;111(1):75-87. doi: 10.1007/s00439-002-0763-x. Epub 2002 Jun 14.
PubMed 12136239Weiss KM, Clark AG. Linkage disequilibrium and the mapping of complex human traits. Trends Genet. 2002 Jan;18(1):19-24. doi: 10.1016/s0168-9525(01)02550-1.
PubMed 11750696Weiss KM, Buchanan AV. Evolution by phenotype: a biomedical perspective. Perspect Biol Med. 2003 Spring;46(2):159-82. doi: 10.1353/pbm.2003.0032.
PubMed 12721519Fullerton SM, Buchanan AV, Sonpar VA, Taylor SL, Smith JD, Carlson CS, Salomaa V, Stengard JH, Boerwinkle E, Clark AG, Nickerson DA, Weiss KM. The effects of scale: variation in the APOA1/C3/A4/A5 gene cluster. Hum Genet. 2004 Jun;115(1):36-56. doi: 10.1007/s00439-004-1106-x. Epub 2004 Apr 24.
PubMed 15108119
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modeling DNA Diversity in Cardiovascular Health/Disease
- ClinicalTrials.gov ID
- NCT00005490
- Acronym / sponsor ID
- 5007
- Conditions
- Cardiovascular Diseases, Heart Diseases
- Study type
- Observational
- Recruitment status
- Completed
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- Aug 1997
- Study completion
- Jun 2003 (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 identify and measure DNA sequence variation in 13 genes that play a central role in key physiological functions involved in the development of cardiovascular disease, that is, genes involved in lipid metabolism, carbohydrate metabolism, and blood pressure regulation.
Detailed description
BACKGROUND:
One of the most complex and challenging problems in human biology and medicine is defining the relationship between DNA sequence variation and interindividual variation in quantitative risk factors for complex diseases having a multifactorial etiology. As the knowledge about the basic human DNA sequence increases, so will the need to define the range of natural variation in human populations and to explore the relationship between nucleotide diversity and phenotype variation in measures of human health.
DESIGN NARRATIVE:
The study was a collaborative one involving Dr. Deborah Nickerson at the University of Washington, Dr. Kenneth Weiss at Pennsylvania State University, and Dr. Charles Sing of the University of Michigan. Dr. Nickerson identified and measured DNA sequence variation in 13 genes that play a central role in key physiological functions involved in the development of cardiovascular disease. She applied state-of-the-art automated fluorescence-based sequencing and high-throughput DNA genotyping methods to uncover and assess DNA sequence variation in three human populations: non-Hispanic Whites from Rochester, MN (lowCVD risk), African-Americans from Jackson, MS (intermediate CVD risk) and non-Hispanic Whites from North Karelia,Finland (high CVD risk).
Dr. Weiss used the theoretical and statistical approaches of molecular population genetics to characterize the cumulative effects of population history on the amount, distribution, and structure of extant variation in 13 candidate CVD susceptibility genes in three populations. His tests of linkage equilibrium and of homogeneity of the variation across several levels of stratification (among individuals, demographic variables, parts of genes, populations, and among genes) further sharpened the understanding of the nature of human genetic variation, particularly with respect to candidate CVD susceptibility genes. He made inferences about functional constraints from gene trees and from patterns of divergence among human populations and between humans and the chimpanzee. Dr. Weiss's project provided the inferential engine that drove the sampling design and sample selection in Dr. Nickerson's project and provided the demographic/historical background necessary for genotype-phenotype inferences of Dr. Sing's project.
Dr. Sing developed models for the relationships between the DNA sequence variation in the 13 candidate CVD susceptibility genes identified, measured, and characterized in Dr. Nickerson's and Dr. Weiss's projects and variation in established quantitative risk factors for CVD, including total plasma cholesterol, HDL cholesterol, and triglycerides, and systolic and diastolic blood pressure collected from the 1,500 individuals. His project established which subset of DNA sequence variations in which candidate genes were associated with variation in CVD risk factors in which subset of individuals and in which of three populations. His elucidation of the relationships between DNA sequence variations and variations in intermediate biological risk factor traits revealed opportunities for intervention to alter the risk of CVD and establish whether such efforts should be directed across populations, within a population, or at an individual.
The study completion date listed in this record was obtained from the "End Date" entered in the old format Protocol Registration and Results System (PRS).
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 7 Nov 2016.
- Background: PubMed 10631137Templeton AR, Clark AG, Weiss KM, Nickerson DA, Boerwinkle E, Sing CF. Recombinational and mutational hotspots within the human lipoprotein lipase gene. Am J Hum Genet. 2000 Jan;66(1):69-83. doi: 10.1086/302699.
- Background: PubMed 10319862Rieder MJ, Taylor SL, Clark AG, Nickerson DA. Sequence variation in the human angiotensin converting enzyme. Nat Genet. 1999 May;22(1):59-62. doi: 10.1038/8760.
- Background: PubMed 9662394Nickerson DA, Taylor SL, Weiss KM, Clark AG, Hutchinson RG, Stengard J, Salomaa V, Vartiainen E, Boerwinkle E, Sing CF. DNA sequence diversity in a 9.7-kb region of the human lipoprotein lipase gene. Nat Genet. 1998 Jul;19(3):233-40. doi: 10.1038/907.
- Background: PubMed 10738543Nelson MR, Kardia SL, Ferrell RE, Sing CF. Influence of apolipoprotein E genotype variation on the means, variances, and correlations of plasma lipids and apolipoproteins in children. Ann Hum Genet. 1999 Jul;63(Pt 4):311-28. doi: 10.1046/j.1469-1809.1999.6340311.x.
- Background: PubMed 10668927Stengard JH, Kardia SL, Tervahauta M, Ehnholm C, Nissinen A, Sing CF. Utility of the predictors of coronary heart disease mortality in a longitudinal study of elderly Finnish men aged 65 to 84 years is dependent on context defined by Apo E genotype and area of residence. Clin Genet. 1999 Nov;56(5):367-77. doi: 10.1034/j.1399-0004.1999.560505.x.
- Background: PubMed 9974428Kardia SL, Haviland MB, Ferrell RE, Sing CF. The relationship between risk factor levels and presence of coronary artery calcification is dependent on apolipoprotein E genotype. Arterioscler Thromb Vasc Biol. 1999 Feb;19(2):427-35. doi: 10.1161/01.atv.19.2.427.
- Background: PubMed 9760210Stengard JH, Weiss KM, Sing CF. An ecological study of association between coronary heart disease mortality rates in men and the relative frequencies of common allelic variations in the gene coding for apolipoprotein E. Hum Genet. 1998 Aug;103(2):234-41. doi: 10.1007/s004390050811.
- Background: PubMed 11042151Nickerson DA, Taylor SL, Fullerton SM, Weiss KM, Clark AG, Stengard JH, Salomaa V, Boerwinkle E, Sing CF. Sequence diversity and large-scale typing of SNPs in the human apolipoprotein E gene. Genome Res. 2000 Oct;10(10):1532-45. doi: 10.1101/gr.146900.
- Background: PubMed 10986041Fullerton SM, Clark AG, Weiss KM, Nickerson DA, Taylor SL, Stengard JH, Salomaa V, Vartiainen E, Perola M, Boerwinkle E, Sing CF. Apolipoprotein E variation at the sequence haplotype level: implications for the origin and maintenance of a major human polymorphism. Am J Hum Genet. 2000 Oct;67(4):881-900. doi: 10.1086/303070. Epub 2000 Sep 13.
- Background: PubMed 11063700Templeton AR, Weiss KM, Nickerson DA, Boerwinkle E, Sing CF. Cladistic structure within the human Lipoprotein lipase gene and its implications for phenotypic association studies. Genetics. 2000 Nov;156(3):1259-75. doi: 10.1093/genetics/156.3.1259.
- Background: PubMed 12165926Stengard JH, Clark AG, Weiss KM, Kardia S, Nickerson DA, Salomaa V, Ehnholm C, Boerwinkle E, Sing CF. Contributions of 18 additional DNA sequence variations in the gene encoding apolipoprotein E to explaining variation in quantitative measures of lipid metabolism. Am J Hum Genet. 2002 Sep;71(3):501-17. doi: 10.1086/342217. Epub 2002 Aug 5.
- Background: PubMed 12136239Fullerton SM, Clark AG, Weiss KM, Taylor SL, Stengard JH, Salomaa V, Boerwinkle E, Nickerson DA. Sequence polymorphism at the human apolipoprotein AII gene ( APOA2): unexpected deficit of variation in an African-American sample. Hum Genet. 2002 Jul;111(1):75-87. doi: 10.1007/s00439-002-0763-x. Epub 2002 Jun 14.
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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.
Deborah Nickerson
University of Washington
Charles Sing
University of Michigan
Kenneth Weiss
Penn State University
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 7 Nov 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 NCT00005490, which also lists 15 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 7 Nov 2016.