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Genetic susceptibility to endomyocardial fibrosis.

Beaton A, Sable C, Brown J, Hoffman J, Mungoma M, Mondo C, Cereb N, Brown C, Summar M, Freers J, Ferreira MB, Yacoub M, Mocumbi AO - Glob Cardiol Sci Pract (2014)

Bottom Line: The human leukocyte antigen (HLA) system is associated with predisposition to various diseases.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.

View Article: PubMed Central - PubMed

Affiliation: Children's National Medical Center, Washington, DC.

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.

No MeSH data available.


Related in: MedlinePlus

Endomyocardial fibrosis of the right ventricle. 1A: Echocardiogram in apical 4-chamber view with characteristic features of (O) obliteration and (R) retraction of the right ventricle with reduction of the right ventricular cavity size. Notice thickening of the tricuspid valve, dilatation of the right atrium and pericardial effusion 1B: Echocardiogram in paraternal short axis view shows a large fibrotic plaque with marked fibrosis and calcification. Again, noted are the enlarged right atrium and large pericardial effusion.
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fig1: Endomyocardial fibrosis of the right ventricle. 1A: Echocardiogram in apical 4-chamber view with characteristic features of (O) obliteration and (R) retraction of the right ventricle with reduction of the right ventricular cavity size. Notice thickening of the tricuspid valve, dilatation of the right atrium and pericardial effusion 1B: Echocardiogram in paraternal short axis view shows a large fibrotic plaque with marked fibrosis and calcification. Again, noted are the enlarged right atrium and large pericardial effusion.

Mentions: The diagnosis of EMF was confirmed using a previously published evaluation scale (Table 1)8 shown to have high reliability and validity for moderate to severe EMF when compared to surgical pathology and direct visualization20. Subjects who scored < 8 were classified as having mild EMF, 8–15 moderate EMF, and >15 severe disease. Only subjects with severe EMF were included in this analysis in order to strengthen the clinical phenotype. Distribution of EMF was recorded as bi-ventricular when lesions involved both ventricles without predominance of one side, right-ventricular when lesions affected only or predominately only the right ventricle, or left-ventricular when lesions affected only or predominately only the left ventricle. A representative echocardiographic image of right-sided EMF can be seen in Figure 1A/B.


Genetic susceptibility to endomyocardial fibrosis.

Beaton A, Sable C, Brown J, Hoffman J, Mungoma M, Mondo C, Cereb N, Brown C, Summar M, Freers J, Ferreira MB, Yacoub M, Mocumbi AO - Glob Cardiol Sci Pract (2014)

Endomyocardial fibrosis of the right ventricle. 1A: Echocardiogram in apical 4-chamber view with characteristic features of (O) obliteration and (R) retraction of the right ventricle with reduction of the right ventricular cavity size. Notice thickening of the tricuspid valve, dilatation of the right atrium and pericardial effusion 1B: Echocardiogram in paraternal short axis view shows a large fibrotic plaque with marked fibrosis and calcification. Again, noted are the enlarged right atrium and large pericardial effusion.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4355520&req=5

fig1: Endomyocardial fibrosis of the right ventricle. 1A: Echocardiogram in apical 4-chamber view with characteristic features of (O) obliteration and (R) retraction of the right ventricle with reduction of the right ventricular cavity size. Notice thickening of the tricuspid valve, dilatation of the right atrium and pericardial effusion 1B: Echocardiogram in paraternal short axis view shows a large fibrotic plaque with marked fibrosis and calcification. Again, noted are the enlarged right atrium and large pericardial effusion.
Mentions: The diagnosis of EMF was confirmed using a previously published evaluation scale (Table 1)8 shown to have high reliability and validity for moderate to severe EMF when compared to surgical pathology and direct visualization20. Subjects who scored < 8 were classified as having mild EMF, 8–15 moderate EMF, and >15 severe disease. Only subjects with severe EMF were included in this analysis in order to strengthen the clinical phenotype. Distribution of EMF was recorded as bi-ventricular when lesions involved both ventricles without predominance of one side, right-ventricular when lesions affected only or predominately only the right ventricle, or left-ventricular when lesions affected only or predominately only the left ventricle. A representative echocardiographic image of right-sided EMF can be seen in Figure 1A/B.

Bottom Line: The human leukocyte antigen (HLA) system is associated with predisposition to various diseases.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.

View Article: PubMed Central - PubMed

Affiliation: Children's National Medical Center, Washington, DC.

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.

No MeSH data available.


Related in: MedlinePlus