Writing in Nature, the researchers said the variant of the IFITM3 gene was much more common in people hospitalized for flu than in the general population.
It controls a malformed protein, which makes cells more susceptible to viral infection.
Experts said those with the flaw could be given the flu jab, like other at-risk groups.
Researchers removed the gene from mice. They found that when they developed flu, their symptoms were much worse than those seen in mice with the gene.
Evidence from genetic databases covering thousands of people showed the flawed version of the gene is presentin around one in 400 people.
The scientists, who came from the UK and US, then sequenced the IFITM3 genes of 53 patients who were in hospital with flu.
Three were found to have the variant – a rate of one in 20.
The researchers say these findings now need to be replicated in bigger studies. And they add it is probably only part of the genetic jigsaw that determines a person’s response to flu.
Professor Paul Kellam of the Wellcome Trust Sanger Institute, who co-led the research, said: “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.
It vindicates our conviction that there is something unusual about these patients”
End Quote Professor Peter Openshaw, Imperial College London
“This is the idea here.”
But he said having this variant would not make any difference to how people were treated.
Prof Kellam added: “Our research is important for people who have this variant as we predict their immune defenses could be weakened to some virus infections.
“Ultimately as we learn more about the genetics of susceptibility to viruses, then people can take informed precautions, such as vaccination to prevent infection.”
Professor Peter Openshaw, director of the Centre for Respiratory Infection at Imperial College London, said: “This new discovery is the first clue from our detailed study of the devastating effects of flu in hospitalised patients.
Sir Mark Walport, director of the Wellcome Trust, said: “During the recent swine flu pandemic, many people found it remarkable that the same virus could provoke only mild symptoms in most people, while, more rarely, threatening the lives of others.
“This discovery points to a piece of the explanation: genetic variations affect the way in which different people respond to infection.
“This important research adds to a growing scientific understanding that genetic factors affect the course of disease in more than one way. Genetic variations in a virus can increase its virulence, but genetic variations in that virus’s host – us – matter greatly as well.” …