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CompletedNCT00007410Updated Jul 29, 2016

Genetic Architecture of Plasma T-PA and PAI-1

An observational study in Cardiovascular Diseases, Heart Diseases and Thrombosis, sponsored by National Heart, Lung, and Blood Institute (NHLBI). Completed. Open to participants aged Up to 100 Years. Per ClinicalTrials.gov, last updated 2016-07-29.

Sponsored by National Heart, Lung, and Blood Institute (NHLBI) · Observational

Study type
Observational
Ages
Up to 100 Years
Sex
All
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Study summary

To determine the effects of six genes on thrombotic risk factors known to be associated with the development of heart disease.

Read the detailed description

BACKGROUND:

Abnormalities in the plasminogen activator system have been implicated in the pathogenesis of arterial and cerebral thrombosis. In particular, elevated plasma levels of plasminogen activator inhibitor-1 (PAI-1), tissue-type plasminogen activator (t-PA), and t-PA/PAI-1 complexes have been found to correlate with increased risk of myocardial infarction (MI) and/or stroke. Vascular fibrinolytic balance is, to a large part, determined by the competing effects of t-PA and PAI-1, and reflects a complex interplay between genetic and environmental factors. The present collaboration focuses on the common hypothesis that the association between activation of the renin-angiotensin-aldosterone system (RAAS) and atherothrombotic events derives from an interaction between the RAAS and the fibrinolytic system.

The study is part of an initiative "Thrombosis of the Arterial and Cerebral Vasculature: New Molecular Genetic Concepts for Prevention and Treatment" which was released in April 1999. The objective of the initiative is to establish collaborative teams of closely interacting investigators with diverse, complementary areas of expertise to elucidate the molecular genetic mechanisms of thrombosis in the arterial and cerebral vasculature.

DESIGN NARRATIVE:

The investigators will use two population-based samples of unrelated individuals to address their aims: 1) study subjects in the PREVEND study in Groningen, The Netherlands in whom DNA and plasma samples and clinical data have already been collected and 2) an estimated 2000 unrelated study subjects from Ghana, Africa in whom data need to be collected. The collaborative study focuses on the common hypothesis that the association between activation of the renin-angiotensin-aldosterone system (RAAS) and atherothrombotic events derives from an interaction between the RAAS and the fibrinolytic system.

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Conditions studied

  • Cardiovascular Diseases
  • Heart Diseases
  • Thrombosis
  • Atherosclerosis
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In context

Cardiovascular Diseases

4,904 studies on the registry are indexed under Cardiovascular Diseases; 919 are open to participants now.

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Lead sponsor

National Heart, Lung, and Blood Institute (NHLBI) is the lead sponsor of 1,117 studies on the registry; 71 are open to participants now.

Of its 57 completed or terminated interventional studies of FDA-regulated products, 49 (86%) have results posted.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
Up to 100 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

No eligibility criteria

05

Study design

06

Study locations

No study locations are listed for this record.

07

References and documents

Publications

  • Moore JH, Williams SM. New strategies for identifying gene-gene interactions in hypertension. Ann Med. 2002;34(2):88-95. doi: 10.1080/07853890252953473. PubMed 12108579 ↗
  • Hahn LW, Ritchie MD, Moore JH. Multifactor dimensionality reduction software for detecting gene-gene and gene-environment interactions. Bioinformatics. 2003 Feb 12;19(3):376-82. doi: 10.1093/bioinformatics/btf869. PubMed 12584123 ↗
  • Ritchie MD, Hahn LW, Moore JH. Power of multifactor dimensionality reduction for detecting gene-gene interactions in the presence of genotyping error, missing data, phenocopy, and genetic heterogeneity. Genet Epidemiol. 2003 Feb;24(2):150-7. doi: 10.1002/gepi.10218. PubMed 12548676 ↗
  • Moore JH, Smolkin ME, Lamb JM, Brown NJ, Vaughan DE. The relationship between plasma t-PA and PAI-1 levels is dependent on epistatic effects of the ACE I/D and PAI-1 4G/5G polymorphisms. Clin Genet. 2002 Jul;62(1):53-9. doi: 10.1034/j.1399-0004.2002.620107.x. PubMed 12123488 ↗
  • Coffey CS, Hebert PR, Krumholz HM, Morgan TM, Williams SM, Moore JH. Reporting of model validation procedures in human studies of genetic interactions. Nutrition. 2004 Jan;20(1):69-73. doi: 10.1016/j.nut.2003.09.012. No abstract available. PubMed 14698017 ↗
  • Moore JH, Hahn LW. Petri net modeling of high-order genetic systems using grammatical evolution. Biosystems. 2003 Nov;72(1-2):177-86. doi: 10.1016/s0303-2647(03)00142-4. PubMed 14642666 ↗
  • Moore JH. The ubiquitous nature of epistasis in determining susceptibility to common human diseases. Hum Hered. 2003;56(1-3):73-82. doi: 10.1159/000073735. PubMed 14614241 ↗
  • Ritchie MD, White BC, Parker JS, Hahn LW, Moore JH. Optimization of neural network architecture using genetic programming improves detection and modeling of gene-gene interactions in studies of human diseases. BMC Bioinformatics. 2003 Jul 7;4:28. doi: 10.1186/1471-2105-4-28. Epub 2003 Jul 7. PubMed 12846935 ↗
  • Williams SM, Ritchie MD, Phillips JA 3rd, Dawson E, Prince M, Dzhura E, Willis A, Semenya A, Summar M, White BC, Addy JH, Kpodonu J, Wong LJ, Felder RA, Jose PA, Moore JH. Multilocus analysis of hypertension: a hierarchical approach. Hum Hered. 2004;57(1):28-38. doi: 10.1159/000077387. PubMed 15133310 ↗
  • Smith MW, Patterson N, Lautenberger JA, Truelove AL, McDonald GJ, Waliszewska A, Kessing BD, Malasky MJ, Scafe C, Le E, De Jager PL, Mignault AA, Yi Z, De The G, Essex M, Sankale JL, Moore JH, Poku K, Phair JP, Goedert JJ, Vlahov D, Williams SM, Tishkoff SA, Winkler CA, De La Vega FM, Woodage T, Sninsky JJ, Hafler DA, Altshuler D, Gilbert DA, O'Brien SJ, Reich D. A high-density admixture map for disease gene discovery in african americans. Am J Hum Genet. 2004 May;74(5):1001-13. doi: 10.1086/420856. Epub 2004 Apr 14. PubMed 15088270 ↗
  • Moore JH, Ritchie MD. STUDENTJAMA. The challenges of whole-genome approaches to common diseases. JAMA. 2004 Apr 7;291(13):1642-3. doi: 10.1001/jama.291.13.1642. No abstract available. PubMed 15069055 ↗
  • Tsai CT, Lai LP, Lin JL, Chiang FT, Hwang JJ, Ritchie MD, Moore JH, Hsu KL, Tseng CD, Liau CS, Tseng YZ. Renin-angiotensin system gene polymorphisms and atrial fibrillation. Circulation. 2004 Apr 6;109(13):1640-6. doi: 10.1161/01.CIR.0000124487.36586.26. Epub 2004 Mar 15. PubMed 15023884 ↗
  • Zeng C, Sanada H, Watanabe H, Eisner GM, Felder RA, Jose PA. Functional genomics of the dopaminergic system in hypertension. Physiol Genomics. 2004 Nov 17;19(3):233-46. doi: 10.1152/physiolgenomics.00127.2004. PubMed 15548830 ↗
  • Moore JH. Computational analysis of gene-gene interactions using multifactor dimensionality reduction. Expert Rev Mol Diagn. 2004 Nov;4(6):795-803. doi: 10.1586/14737159.4.6.795. PubMed 15525222 ↗
  • Thornton-Wells TA, Moore JH, Haines JL. Genetics, statistics and human disease: analytical retooling for complexity. Trends Genet. 2004 Dec;20(12):640-7. doi: 10.1016/j.tig.2004.09.007. PubMed 15522460 ↗
  • Robinson M, Williams SM. Role of two angiotensinogen polymorphisms in blood pressure variation. J Hum Hypertens. 2004 Dec;18(12):865-9. doi: 10.1038/sj.jhh.1001768. PubMed 15343353 ↗
  • Hahn LW, Moore JH. Ideal discrimination of discrete clinical endpoints using multilocus genotypes. In Silico Biol. 2004;4(2):183-94. PubMed 15107022 ↗
  • Moore JH, Boczko EM, Summar ML. Connecting the dots between genes, biochemistry, and disease susceptibility: systems biology modeling in human genetics. Mol Genet Metab. 2005 Feb;84(2):104-11. doi: 10.1016/j.ymgme.2004.10.006. Epub 2004 Dec 19. PubMed 15670716 ↗
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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 29, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT00007410
Lead sponsor
National Heart, Lung, and Blood Institute (NHLBI)
First posted
Dec 19, 2000
Start date
Sep 2000
Primary completion
Jul 2006
Completion
Jul 2006
Last update
Jul 29, 2016

Study contacts

Jason Moore
Vanderbilt University
View the source record on ClinicalTrials.gov ↗

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