Genetic flaw raises flu risk

Differences in the severity of people's flu symptoms may be due to a genetic variant, according to scientists.

Normally the gene in question, IFITM3, produces a protein that stops the flu virus invading cells. Researchers found that when mice without this gene were exposed to the flu virus they suffered more critical symptoms, such as severe pneumonia, than normal mice. The virus also replicated ten times more than in the normal mice and penetrated deeper into the lungs.

In the general European population, around one in 400 people have a mutated version of IFITM3 that produces less of the protective protein. However, when the team analysed the genomes of 53 patients who had been hospitalised due to a flu infection, they found that one in 20 had the mutation.

Furthermore, people in intensive care with severe pandemic or seasonal flu in the UK were 17 times more likely to have a mutated version of IFITM3, when compared to Europeans in general.

This evidence suggests the gene plays a critical role in determining how vulnerable people will be to infection.

Co-author Professor Paul Kellam of the Wellcome Trust Sanger Institute acknowledged that since not all patients with severe symptoms carry the variant gene, it clearly is not the only factor to take into consideration.

'At the moment, if someone is in a more vulnerable group because of co-morbidity [another health problem], they would be offered the flu vaccine', he told the BBC. 'Our research is important for people who have this variant as we predict their immune defences could be weakened to some virus infections'.

The study, published in Nature, also reports that the IFITM3 gene became more widespread in humans around 10,000 years ago. This coincides with the time humans are thought to have first caught the flu, from livestock, suggesting it is part of an evolutionary adaptation to the emergence of the flu virus.

Analysis of IFITM3 may lead to patient screening to identify those who are potentially more vulnerable, making them a priority for vaccination. It may also help to design new vaccines against different types of viruses, not just influenza.