Cold and Flu : How Genetics Determine Flu Risk

Helen McArdle

BREAKTHROUGH discovery by Scots researchers could reveal why some people are more likely to die from flu than others.

A collaborative study by scientists at Edinburgh University's Roslin Institute and clinicians at NHS Lothian has shown people not protected by a certain gene are at risk of potentially life- threatening reactions to the viruses.

It is the first time researchers have identified a gene which determines our susceptibility and response to flu and other infections, and could pave the way for a screening regime to identify individuals who would benefit from vaccination.

Professor Tim Walsh, a consultant and professor of critical care medicine at Edinburgh University, said: "Flu can be devastating in the very young and elderly, but some previously fit young people can also develop life-threatening lung problems.

"Many young people required prolonged periods in intensive care during the swine flu pandemic and we had little idea why this small number of people was so severely affected. This study provides some clues as to why this may happen.

"It opens avenues for research to develop ways of predicting who might be at risk and where to focus efforts to find new treatments for severe viral infections."

The gene - known as IFITM3 - produces a protein that protects cells against infections. It is believed to be vital for kick- starting the immune system's battle against viruses such as swine flu. When present in large quantities, the protein hinders the spread of the flu virus in the lungs. However, people with the variant form of the gene cannot produce as much of this defence protein, thereby leading to a more severe bout of flu.

The study, published in the journal Nature, found patients who ended up in intensive care with potentially fatal complications after developing flu were much more likely to have a variant of this gene, which did not protect against the virus.

The study analysed DNA from patients treated in Scottish intensive care units during the 2009/10 swine flu pandemic. Blood samples were taken from the patients who had been previously fit and healthy.

While the variant is found in only 0.3% of the population, the scientists found it was present in 5.3% of patients in intensive care with flu - suggesting it plays a highly significant role in causing otherwise healthy individuals to fall seriously ill.

Dr Kenneth Baillie, of the Roslin Institute, said: "While most people who contract flu during a pandemic will recover well and not experience serious symptoms, some develop a catastrophic and potentially fatal illness and need to be treated in intensive care. This happens to otherwise healthy, young people.

"The answer as to why some people become seriously affected by flu and others don't was a mystery, but this study shows for the first time it may be because they are more genetically susceptible to the virus."

The study, launched after the swine flu pandemic arrived in Scotland in 2009, followed initial research on mice carried out at the Wellcome Trust Sanger Institute near Cambridge.

The Cambridge studies had already indicated mice with the rarer, mutant version of IFITM3 were much more likely to have severe symptoms than mice with the normal version. Now the Scottish research has shown a parallel relationship between flu and the human genome.

Professor Paul Kellam, a co-author on the paper and based at the Wellcome Trust Sanger Institute, said: "This is important for people who have this variant as we predict their immune infections defences could be weakened to some virus infections.

"Ultimately, as we learn more about the genetics of susceptibility to viruses, these people can take informed precautions, such as vaccinations to prevent infection."

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