title: Genetic susceptibility to endomyocardial fibrosis.
abstract: BACKGROUND
  Endomyocardial fibrosis (EMF) is the most common form of restrictive cardiomyopathy worldwide. It has been linked to poverty and various environmental factors, but-for unknown reasons-only some people who live in similar conditions develop the disease. EMF cases cluster within both families and ethnic groups, suggesting a role for a genetic factor in host susceptibility. The human leukocyte antigen (HLA) system is associated with predisposition to various diseases. This two-center study was designed to investigate variation in the HLA system between EMF patients and unaffected controls. We provide the first genetic investigation of patients with EMF, as well as a comprehensive review of the literature.
  
  
  METHODS
  HLA class I (HLA-A, -B, -C) and class II (DRB1, DQB1) types were determined in 71 patients with severe EMF and 137 controls from Uganda and Mozambique. Chi Square analysis was used to identify any significant difference in frequency of class I and class II HLA types between cases and controls.
  
  
  RESULTS
  Compared to ethnically matched controls, HLA-B*58 occurred more frequently in Mozambique patients with EMF and HLA-A*02:02 occurred more frequently in Ugandan patients with EMF.
  
  
  CONCLUSIONS
  Ample subjective evidence in the historical literature suggests the importance of a genetically susceptible host in EMF development. In this first formal genetic study, we found HLA alleles associated with cases of EMF in two populations from sub-Saharan Africa, with EMF patients being more likely than controls to have the HLA-B*58 allele in Mozambique (p-0.03) and the HLA-A*02:02 in Uganda (p = 0.005). Further investigations are needed to more fully understand the role of genetics in EMF development.
authors.affiliation: Children's National Medical Center, Washington, DC.
authors.forename: Andrea
authors.initials: A
authors.lastname: Beaton
authors.affiliation: Children's National Medical Center, Washington, DC.
authors.forename: Craig
authors.initials: C
authors.lastname: Sable
authors.affiliation: NHS Blood and Transplant, Colindale, England.
authors.forename: Juliette
authors.initials: J
authors.lastname: Brown
authors.affiliation: Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Joshua
authors.initials: J
authors.lastname: Hoffman
authors.affiliation: Mulago Hospital, Kampala, Uganda.
authors.forename: Michael
authors.initials: M
authors.lastname: Mungoma
authors.affiliation: Mulago Hospital, Kampala, Uganda.
authors.forename: Charles
authors.initials: C
authors.lastname: Mondo
authors.affiliation: Histogenetics.
authors.forename: Nezith
authors.initials: N
authors.lastname: Cereb
authors.affiliation: NHS Blood and Transplant, Colindale, England.
authors.forename: Colin
authors.initials: C
authors.lastname: Brown
authors.affiliation: Children's National Medical Center, Washington, DC.
authors.forename: Marshall
authors.initials: M
authors.lastname: Summar
authors.affiliation: Mulago Hospital, Kampala, Uganda.
authors.forename: Jurgen
authors.initials: J
authors.lastname: Freers
authors.affiliation: Instituto do Coração, Mozambique.
authors.forename: Maria Beatriz
authors.initials: MB
authors.lastname: Ferreira
authors.forename: Magdi
authors.initials: M
authors.lastname: Yacoub
authors.forename: Ana Olga
authors.initials: AO
authors.lastname: Mocumbi
keywords: Cardiomyopathy; Endomyocardial Fibrosis; Genetic Suceptibility