Heart failure gene more common in south asia

Heart failure gene more common in south asia

Scientists have discovered a variant of a gene that increases the risk heart failure seven-fold is most common amongst people in South East Asia, where the disease is a leading cause of death.

The study was the work of an international team of 25 scientists from four countries and was published online in the 18 January issue of Nature Genetics.

Heart disease kills more people around the world than any other disease, and nowhere is this more evident than in India, about which the researchers note that by 2010, about 60 per cent of the world's heart disease will be in India. There are many causes, some genetic and some linked to lifestyle, and they are hard to pin down, but this study reveals a remarkable large effect from one simple genetic cause.

The results of this study explain why: across the world as a whole, 1 person in 100 carries a mutation of a gene that is most likely to result in heart problems, but in India, the mutation is four times more common: it is carried by 4 people out of every 100.

The mutation is a deletion of 25 base pairs in a sequence that codes for the heart protein MYBPC3 (a base pair is a unit of DNA comprising two of the four types of nucleotide A, T, G, C: the human genome has 20,000 to 25,000 genes made up of 3 billion base pairs). The deletion appears to occur almost exclusively in people from the Indian subcontinent.

The mutation itself is not a new find: it was discovered about five years ago in two Indian families with a high rate of heart failure (cardiomyopathy, caused by a weakness in the heart muscle). It wasn't until this study, which investigated nearly 1,500 people from different parts of India, that its importance was realized.

For the study, the researchers, led by Kumarasamy Thangaraj from the Centre for Cellular and Molecular Biology, Hyderabad, India, looked for this particular mutation in 800 people with cardiomyopathy and 700 that did not have the disease (the controls). They found that the risk of heart disease among people with the mutation was 7 times that of people without it, practically guaranteeing they would develop the condition.

People who carry this mutation often don't have any symptoms until they reach middle age, but then most experience a range of symptoms and some die of heart failure.

Thangaraj explained that the deletion of the 25 base pairs means that the MYBPC3 heart protein forms abnormally:

"Young people can degrade the abnormal protein and remain healthy, but as they get older it builds up and eventually results in the symptoms we see," said Thangaraj.

Co-author Chris Tyler-Smith from the Wellcome Trust Sanger Institute, Hinxton, UK said the mutation was unique in that it is unusual to find such a harmful genetic effect surviving down the generations. It's probably because the effect only develops after most people have had their children, so there is no natural selection effect taking place which is how most harmful genes "die out". Tyler-Smith called it a "case of chance genetic drift: simply terribly bad luck for the carriers".

Perundurai S. Dhandapany from Madurai Kamaraj University, Madurai, India, said that while it was bad news "that many of these mutation carriers have no warning that they are in danger," the good news was that "we now know the impact of this mutation".

Director of the Wellcome Trust, Sir Mark Walport said this was a very important finding:

"Heart disease is one of the world's leading killers, but now that researchers have identified this common mutation, carried by one in 25 people of Indian origin, we have hope of reducing the burden that the disease causes."

He said this finding opened the door to better screening and it may also lead to new treatments.

The finding raises the notion that perhaps new drugs could be developed that destroy or speed up destruction of the abnormal protein and thus postpone the start of symptoms. The researchers suggested there are some 60 million people affected by this mutation worldwide, forming a very large target population for such a treatment.

"A common MYBPC3 (cardiac myosin binding protein C) variant associated with cardiomyopathies in South Asia.

Perundurai S Dhandapany, Sakthivel Sadayappan, Yali Xue, Gareth T Powell, Deepa Selvi Rani et al.

Nature Genetics Published online Jan 18, 2009.


Click here for Abstract.

Sources: Journal abstract, Wellcome Trust Sanger Institute.

South Asians and Heart Disease - Creative Solutions with Therapeutic Lifestyle Changes (Video Medical And Professional 2020).

Section Issues On Medicine: Cardiology