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    Genetic susceptibility to endomyocardial fibrosis

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    Date
    2014
    Author
    Andrea Beaton M.D
    Craig Sable M.D
    Juliette Brown PhD
    Joshua Hoffman
    Michael Mungoma M.D.
    Charles Mondo M.D.
    Nezith Cereb
    Colin Brown PhD
    Marshall Summar M.D
    Jurgen Freers M.D
    Maria Beatriz Ferreira MD
    Magdi Yacoub M.D
    Ana Olga Mocumbi M.D.
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    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 ¼ 0.005). Further investigations are needed to more fully understand the role of genetics in EMF development.
    URI
    http://hdl.handle.net/123456789/5590
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