Gene variants may raise risk of infectious diseases

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Scientists have found a group of gene variants that increase susceptibility to infectious diseases like tuberculosis and malaria and say the discovery may help in designing new drugs to tackle several illnesses at once.

Researchers from Britain and Singapore found that several different mutations of a gene called CISH are linked to a higher risk of contracting infectious diseases.

Having just one of these mutations can raise the risk by 18 percent, they said.

"That one small gene can be involved in multiple infectious diseases at a very fundamental level is a rare and unexpected finding,” said Judith Swain, director of the Singapore Institute for Clinical Sciences, whose researchers worked on the study.

She said the discovery had “far-reaching implications” because it added to scientists’ understanding of the mechanisms of infectious disease, which in turn would help the search for new and more effective medicines.

Although there are drugs available to treat them, malaria, tuberculosis (TB) and bacterial blood infections still kill millions of people around the world.

According to the World Health Organization, malaria and TB combined kill almost 2.7 million people every year.

The vast majority of deaths are in poorer countries where access to prevention steps and medicines is limited, and experts say new treatments and vaccines are needed to save lives.

This team of scientists analyzed genes from more than 8,000 people at clinical sites in Malawi, Kenya, Vietnam, Hong Kong and The Gambia over a period of five years.

They were looking for genetic variants that might increase susceptibility to TB, malaria and serious bacterial infections of the blood, or bacteraemia.

The results, published in the New England Journal of Medicine on Wednesday, showed a striking link between variants of a gene called CISH and greater risk of susceptibility.

CISH encodes a protein that is involved in the immune response to infectious diseases. It plays a role in dampening down messaging signals between cells of the immune system.

“It’s really unusual to find a gene that impacts on several major infectious diseases,” Adrian Hill, who led the study at the Wellcome Trust Center for Human Genetics (CHG) at Oxford University, said in a telephone interview.

“And this is one that’s right at the heart of regulating immune signaling, so that’s why it’s of such great interest.”

Hill and colleagues identified five different genetic variants of the CISH gene.

In the people they studied, having just one of these variants increased susceptibility to disease by 18 percent compared with someone who did not have any of the risk variants.

“That is a substantial effect size for a single gene,” said Fredrik Vannberg of Wellcome’s CHG, who also worked on the study.

The risk increased to 81 percent in people carrying four or more of the CISH gene risk variants, the scientists said.

SOURCE:

New England Journal of Medicine, May 19, 2010.

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