Limits...
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

Distribution of HLA alleles determined to have significance for the 2 populations. 3A: Mozambique; 3B: Uganda.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4355520&req=5

fig3: Distribution of HLA alleles determined to have significance for the 2 populations. 3A: Mozambique; 3B: Uganda.

Mentions: Table 3 shows selected HLA-A, -B frequencies in the Mozambique patients severe EMF (n = 40) and controls. The frequency of HLA-A*02:02 was comparable in patients and controls. HLA-B*58 was more frequent in patients compared with controls (37.5% vs. 14.6%, p = 0.03, Figure 3a. Patients and controls positive for HLA-B*58 were tested further to determine which allele of HLA-B*58 was present. Although both HLA-B*58:01 and HLA-B*58:02 were both more frequent in the patients than the controls the differences were not significant. The frequencies of the HLA types found in the groups of EMF patients with bi-ventricular EMF (n = 17), right-ventricular EMF (n = 23) were compared. The frequency of HLA-A*02 in patients with bi-ventricular EMF was reduced when compared to patients with right-ventricular EMF (4/17 vs. 8/23, respectively) and the frequency of HLA-B*58 in patients with bi-ventricular EMF was increased when compared to patients with right-ventricular EMF (8/17 vs. 7/23 respectively) but neither difference is statistically significant.


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)

Distribution of HLA alleles determined to have significance for the 2 populations. 3A: Mozambique; 3B: Uganda.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig3: Distribution of HLA alleles determined to have significance for the 2 populations. 3A: Mozambique; 3B: Uganda.
Mentions: Table 3 shows selected HLA-A, -B frequencies in the Mozambique patients severe EMF (n = 40) and controls. The frequency of HLA-A*02:02 was comparable in patients and controls. HLA-B*58 was more frequent in patients compared with controls (37.5% vs. 14.6%, p = 0.03, Figure 3a. Patients and controls positive for HLA-B*58 were tested further to determine which allele of HLA-B*58 was present. Although both HLA-B*58:01 and HLA-B*58:02 were both more frequent in the patients than the controls the differences were not significant. The frequencies of the HLA types found in the groups of EMF patients with bi-ventricular EMF (n = 17), right-ventricular EMF (n = 23) were compared. The frequency of HLA-A*02 in patients with bi-ventricular EMF was reduced when compared to patients with right-ventricular EMF (4/17 vs. 8/23, respectively) and the frequency of HLA-B*58 in patients with bi-ventricular EMF was increased when compared to patients with right-ventricular EMF (8/17 vs. 7/23 respectively) but neither difference is statistically significant.

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