Genetic Architecture of Heart Disease in Rural Brazil

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00023556
Recruitment Status : Completed
First Posted : September 7, 2001
Last Update Posted : July 12, 2016
Information provided by:
National Heart, Lung, and Blood Institute (NHLBI)

Brief Summary:
To examine the genetics of human susceptibility to Chagas' disease, a leading cause of heart disease throughout Latin America.

Condition or disease
Chagas Disease Heart Diseases Arrhythmia Heart Failure, Congestive

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Detailed Description:


Chagas' disease is a leading cause of heart disease throughout Latin America, affecting between 16 and 18 million individuals. The disease, named after the Brazilian physician Carlos Chagas who first described it in 1909, exists only on the American Continents. It is caused by a flagellate protozoan parasite, Trypanosoma cruzi, transmitted to humans by blood-sucking triatomine insects known popularly in the different countries as "vinchuca", "barbeiro", "chipo" etc. The geographical distribution of the human T.cruzi infection extends from Mexico to the south of Argentina. In Brazil alone, approximately 10 percent of the population is seropositive for T. cruzi. Given the large pool of primary hosts for this zoonotic disease, complete eradication of Chagas' disease through control of the arthropod vector is unlikely. Research with humans and animal models indicates that there is variation in susceptibility to infection, and disease outcome, and that this variation may be due to genetic factors. Thus, this form of heart disease represents a complex phenotype with potential genetic determinants to both susceptibility to infection and differential disease pathogenesis.


The genetic epidemiology project studies an estimated 1,125 Black individuals age 18 years or older from a small community in Posse, Brazil in which the study population may be drawn from as few as four to five large pedigrees with varying blood relationships. Preliminary pilot data appear very promising regarding the primary hypothesis that specific genetic factors influence the susceptibility to this complex zoonotic disease. The investigation will be divided into three parts involving phenotypic characterization, statistical genetic analyses to determine the relative proportion of the phenotypic variance due to additive genetic effects, and localization of genes influencing the development of Chagas' disease.

The phenotypic characterization will involve clinical history, infection status, immunologic studies, and cardiac status. The chronic phase of T. cruzi infection results in Chagas' disease manifest as a cardiomyopathy with heart block, conduction disturbance, ventricular tachyarrhythmia, heart failure, and sudden arrhythmic death. The cardiac phenotyping will involve electrocardiographic time intervals (PR interval, QRS duration, QT interval duration) as well as abnormal patterns (left anterior fascicular block, left ventricular hypertrophy, right bundle branch block), and possibly some measure of heart failure in terms of New York Heart Association functional classification. Right bundle branch block is probably the most frequent early manifestation of chronic cardiac involvement.

The genetic linkage studies will attempt to localize genes influencing susceptibility to T. cruzi infection, ECG parameters (e.g., right bundle branch block), and immunologic factors using markers placed approximately every 10 centimorgans (cM) throughout the genome.

About 375 individuals will be sampled per year. Each subject will donate two 10 ml samples of blood which will be used for immunoassays for seropositivity for T. cruzi, and for genotyping with 382 polymorphic short tandem repeats. During the initial visits, the population subjects will also be interviewed to gather information on demographic, pedigree, and socioeconomic makeup. Additionally, questions on pregnancy status, household ecology (years in the house, rooms shared, pets, rodents, food storage, triatomid bug history, etc) and residence history will be determined during the survey. In the fourth year, the investigators will return to the collection site and administer ECGs on 375 individuals per year.

The blood collected in Brazil will be sent to San Antonio for high-throughput genotyping using 382 polymorphic short tandem repeats (STRs) spread throughout the genome. A population specific 10cM map is expected to be useful for linkage analysis.

Study Type : Observational
Study Start Date : September 2001
Actual Primary Completion Date : August 2008
Actual Study Completion Date : August 2008

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Diseases
U.S. FDA Resources

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
No eligibility criteria

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00023556

Sponsors and Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
OverallOfficial: Sarah Williams-Blangero Southwest Foundation for Biomedical Research

Publications: Identifier: NCT00023556     History of Changes
Other Study ID Numbers: 982
R01HL066480-05 ( U.S. NIH Grant/Contract )
First Posted: September 7, 2001    Key Record Dates
Last Update Posted: July 12, 2016
Last Verified: August 2008

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Chagas Disease
Cardiovascular Diseases
Euglenozoa Infections
Protozoan Infections
Parasitic Diseases