Genes explain susceptibility to a rare heart disease

In the first formal study of its kind, an international team of researchers has identified two different genetic variants that make certain populations in sub-Saharan Africa more susceptible to a form of heart disease that is present throughout the developing world¹.

Endomyocardial fibrosis (EMF) is a progressive cardiomyopathy, or disease of the heart muscle, that is characterized by abnormal changes to the inner lining of the heart ventricles, which leads to narrowing of the heart cavities. Its causes are unknown, but the disease has previously been linked to poverty and various environmental factors.

It develops only in some people but not others, however, and is known to cluster within both families and certain ethnic groups, suggesting that genetic factors play a role in susceptibility to it.

Andrea Beaton of the Children’s National Medical Center in Washington, D.C., and her colleagues therefore examined genes of the human leucocyte antigen (HLA) system in 71 patients with severe EMF and 137 healthy controls, recruited from the Mozambique Heart Center, the Ugandan Heart Institute and the cardiology ward at Mulago Hospital in Uganda.

HLA genes encode the proteins called the human antigen leukocyte complex, which help the immune system distinguish between the body’s own proteins and those produced by viruses, bacteria and other disease-causing microbes. In both of the populations studied, the researchers found that more females than males suffered from EMF, and that the condition predominantly affected the right rather than the left side of the heart.

They also identified two distinct alleles, or variants, of HLA genes, each associated with susceptibility to EMF in one of the populations. One of these, called HLA-A*02:02, occurred more frequently in Ugandan patients with EMF, whereas the other, HLA-B*58, was more prevalent in EMF patients from Mozambique.

“EMF is quite a rare cardiomyopathy compared to others,” says Beaton, “but further investigations should be aimed at confirming that these genetic variants predict susceptibility, and understanding why this is the case.”

HLA genes play an essential role in the functioning of the immune system, and differences in them between individuals can both protect and predispose people to a wide variety of difference diseases. However, exactly how these newly identified genetic variants contribute to the development of EMF is still unclear.

“We still have very little understanding of the cause of EMF,” adds Beaton, “and an understanding of why some people get the disease while others do not could help advance this understanding.”

1. Beaton, A., Sable, C., Brown, J., Hoffman, J., Mungoma, M. et al. Genetic susceptibility to endomyocardial fibrosis. Global Cardiology Sci. Practice 2014, 60. | article