The Genetic Basis of Acquired Heart Disease in Africa
The Genetic Basis of Acquired Heart Disease in Africa
Background:

 - An acquired heart disease is one that a person gets after they are born. Two of these are
 rheumatic heart disease (RHD) and endomyocardial fibrosis (EMF). They are found more commonly
 in people who live in Africa than in other places in the world. Researchers want to learn
 more about these diseases. They especially want to know what role genes and other factors
 play in them.

 Objective:

 - To identify genetic risk factors for RHD and EMF in sub-Saharan Africa.

 Eligibility:

 -  Children and adults with RHD or EMF.

 -  Healthy volunteers over age 10.

 Design:

 -  Participants will come from existing study groups in Uganda and Nigeria.

 -  Participants may be required to provide a sample of their DNA. They will do this with
 either a blood or saliva sample or a swab of the mouth.

 -  Collected samples will be labeled with a code and sent to a lab in the United States for
 analysis. Remaining portions of participants samples will be stored for an unlimited
 period of time. They may be used in future studies.

 -  Some genetic and health information from participants might be placed into one or more
 scientific databases.

 -  Participant names and identifying information will be kept private. But there is a small
 chance someone could trace them from their genetic information.
Recent advances in genomic techniques are making possible a new wave of genetic discovery in
 many complex diseases. However, the genetic risk factors for two forms of acquired heart
 disease that are particularly common in Africa - rheumatic heart disease (RHD) and
 endomyocardial fibrosis (EMF) remains unknown. In this application, we propose to evaluate
 genetic risk factors for rheumatic heart disease (RHD) and endomyocardial fibrosis (EMF). A
 number of factors should facilitate the identification of genetic risk variants underlying
 the two conditions. First, both forms of acquired heart disease are endemic to sub-Saharan
 Africa (SSA). Second, affected patients and those who do not develop the conditions share a
 common environment. Finally, the availability of high density SNP arrays to capture common
 and rare variation makes the characterization of genomic variation better than ever. Patients
 will be enrolled at the Uganda Heart Institute in Kampala, Uganda, and at the College of
 Medicine, University of Lagos, Nigeria, with the potential to include other African sites.
 Genomic studies will be done at the NIH.
-  INCLUSION CRITERIA:

 -  Rheumatic Heart Disease:

 Patients with a definite diagnosis of rheumatic heart disease based on the 2006 World
 Health Organization/National Institutes of Health Joint Criteria
 (http://www.niaid.nih.gov/topics/strepThroat/Documents/groupasequelae.pdf) controls who do
 not meet this criteria. The diagnosis will be made by a cardiologist on our team. The
 method of screening and recruitment will be specific to each of our two sites: Uganda Heart
 Institute and University of Lagos, Nigeria.

 -Uganda Heart Institute:

 --recruitment will be conducted from an existing cohort of patients initially recruited by
 members of our team from 21 randomly selected

 schools in Uganda. Participants meeting the criteria noted above for RHD will be considered
 cases and those who do not will be considered controls. Additionally, parents will be
 invited to participate as controls. For controls, only children over age 10 will be
 considered as this increases the likelihood of exposure

 to S. pyogenes. The initial study was approved by the institutional review boards of the
 Children s National Medical Center (Washington,D.C.), Makerere University (Kampala,
 Uganda), and the

 Ugandan Ministries of Health and Education

 -  University of Lagos:

 --This program will be modeled after the Uganda program. Participants will be screened
 for RHD at the College of Medicine or at randomly selected schools. Participants
 meeting criteria for RHD will be consented as cases and those negative for RHD will be
 consented as controls. Additionally, parents will be invited to participate as
 controls. For controls, only children over age 10 will be considered as this increases
 the likelihood of exposure to S. pyogenes

 -  Endomyocardial Fibrosis (EMF):

 -  Cases: the study will include patients with a diagnosis of EMF based on
 echocardiography, history, and physical exam performed by cardiologist;on our
 team Over 50 patients have been identified at the Uganda Heart Institute with EMF
 and will be contacted for study participation; additionally, newly diagnosed
 patients at the Uganda Heart Institute will be offered participation.

 -  Controls: Geographic and age matched controls will be used for association study.
 Controls will be disease free, based on above criteria. We will exclude controls
 less than 15 years of age based on disease peak around age 10. Controls will be
 selected from those being screening for RHD

 EXCLUSION CRITERIA:

 -Anyone unwilling to provide informed consent (for themselves as adults, or on behalf of
 their children as minors) or assent.