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‘Country boy' hunts for genes that cause heart disease
MRC News
Dr Bongani Mayosi describes himself as a ‘country boy'. But he's a man
with a passionate interest in finding the causes of heart failure – and this
led to a recent discovery of a gene that puts many South Africans at risk.
Born in Umtata and
growing up in Ngqamakhwe, a rural district near Butterworth in the Transkei, Dr
Mayosi always knew medicine would be his mission. As a child, he accompanied his
father (a rural GP later turned obstetrician) on his rounds and saw him
dispensing medicine at the side of the road from the back of a Landrover.
"He practiced community-based medicine well before it became
fashionable!" he jokes. A few years later, Dr Mayosi was the top
matriculant in the Transkei, gaining distinctions in 4 subjects. He entered
medical school at the tender age of 16, and managed to pass both the MB.ChB. and
B.Med.Sci degrees cum laude. "But I knew I wanted to combine clinical work
and research in my career. There were many things that we didn't know and I was
intrigued by that," he says. He then joined Groote Schuur Hospital to train
in internal medicine and cardiology. In 1997 he was awarded an MRC Research
Training Fellowship, and in 1998 he went to Oxford University as a Nuffield
Medical Fellow to read molecular genetics. The research work done during this
time led to the discovery of the gene associated with putting people at risk of
heart failure and was published in the prestigious British journal, Lancet.
Heart failure and genetics
According to Dr Mayosi,
heart attacks are a major cause of heart failure world wide. Such attacks damage
the heart muscle and lead to eventual heart failure. Uncontrolled high blood
pressure and heart valve disease are also important causes of heart disease,
particularly in Africa. But many people suffer from heart failure for no
apparent reason. This condition is known as idiopathic dilated cardiomyopathy.
During his studies at Oxford, Dr Mayosi became interested in the genetic causes
of heart disease. He says that there are two types of genetic diseases. There
are diseases that are caused by a single gene – if you inherit the abnormal
gene from your parents you will certainly develop that disease. Single gene
disorders tend to be uncommon. An example of a single gene disorder is
hypertrophic cardiomyopathy. Then there are diseases or conditions that are
caused by a genetic predisposition – you won't of necessity develop the
disease if you inherit the susceptibility gene, but you will be at higher risk.
"We believe that these susceptibility genes are involved in common diseases
such as heart attack. In addition to environmental factors such as smoking, a
high-fat diet, high blood cholesterol level and lack of exercise, susceptibility
genes play a definite role in the contraction of these conditions. For example,
some people lead a very healthy lifestyle without any environmental risk factors
but they still contract heart disease – and here we suspect that they have an
increased dose of susceptibility genes," explains Dr Mayosi.
Polymorphisms
Dr Mayosi and his colleagues
put their ideas to the test. They recruited patients with idiopathic dilated
cardiomyopathy, and compared their genes to a number of normal, healthy
subjects. "Since the heart is very dependant on a regular supply of energy
to keep it beating, we thought that subtle abnormalities (called polymorphisms)
in the DNA of the mitochondrion or power house of the cells, might lead to the
heart not functioning well," he says. This was one hunch that paid off
handsomely. They found that in South Africans, 45% of the sick patients had
these abnormalities, while only 16% of the ‘normal' population had them.
"We've identified a genetic risk factor which increases the risk of heart
failure two-fold in people who carry the genetic factor," says Dr Mayosi.
They then repeated the experiment with a number of British test subjects totally
different from the South African genetic pool. And the test results were
similar: 17% of the sick subjects carried the polymorphism, compared to only 8%
of the healthy subjects.
Development of new drugs
This was the first
demonstration of its kind in Africa and opens the door to the development of new
ways of thinking about heart failure. "It gives us clues about possible
targets for treatment. We could design drugs that help the cells work better so
that the energy is generated in a more efficient way. There are already drugs
that help to slow down the heartbeat - this new information could help to refine
the use of old tools," says Dr Mayosi. "Genetics is going to help us
to get to the very roots of disease. There is a lot of knowledge about the
environmental factors for heart disease and we need to make use of that
information. But it doesn't look as if we are going to defeat heart disease
solely by addressing environmental factors. We need to find out why the host is
susceptible. And if we combine an environmental and genetic approach, we'll be
successful." Dr Mayosi believes in keeping medicine in the family. His
wife, Nonhlanhla, is a dermatology registrar at Groote Schuur Hospital. There
are also photos of two angelic little girls on his desk. "That's Vuyi and
Gugu – our pride and joy," says this proud dad.
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