Fighting against the flu

Genetic variant is associated with severe flu in the Chinese population

Doi: 10.1038/ncomms2433

C allele at SNP 12252 associated with disease severity in acutely influenza A.

Researchers have found that two out of three patients in China with a severe influenza infection have a genetic variant of the IFITIM3 gene, previously shown to affect the severity of influenza infection in patients in the UK. By contrast, only one in four people in China with mild influenza have this genetic variant.

This variant is more common in the Chinese population compared to Northern Europeans and is associated with the severity of influenza infection rather than susceptibility to the disease.

IFITM3 is an important protein that can efficiently restrict the entry of influenza and other human viruses such as coronavirus, Dengue virus and West Nile virus into human cells. A genetic variant of this gene, rs12252, reduces antiviral activity of IFTIM3 leading to a more severe infection.

“Professor Paul Kellam at the Sanger Institute in Cambridge and Professor Peter Openshaw at Imperial College London discovered this genetic variant was associated with severe influenza infection in Europeans, but this variant is extremely rare in Europeans. We became interested in this because we noticed it is 100 times more common in China.

“It’s vital that we continue to fund research that examines flu from the smallest details of our genetic code and in the populations around the world that continue to be vulnerable to infection.”

Dr Tao Dong Lead author from the MRC Human Immunology Unit, Oxford University

The team examined samples from the 2009 H1N1influenza A pandemic in China. They found a strikingly large number of patients with severe influenza infections, had a CC genotype, or copies of the variant on both chromosomes. People with this CC genotype have a six fold greater risk of severe infection compared to people with other genotypes, or different genetic makeup.

The IFITM3 gene variant could have a strong effect on the distribution and control of influenza in China and in people of Chinese decent. This finding could help identify those at high risk of severe infection and help to prioritise those in highest need of treatment.

“Understanding why some people may be more severely affected by influenza than others is crucial in improving our ability to manage flu epidemics and potentially to prevent people dying from the virus. This research is important for the people who have this variant. Large scale testing of influenza patients for this variant, especially in Chinese hospitals, is now needed to determine the significance and utility of this variant for the prognosis, early intensification of treatments and prioritising of people for vaccinations.”

Professor Paul Kellam Co-author from the Wellcome Trust Sanger Institute

More information

Funding

The work was supported by: the Beijing Natural Science Foundation Beijing, Municipal Science and Technology, National S&T Major Project for Infectious Diseases Control, Beijing Youan Hepatitis/AIDS foundation, National Natural Science Foundation of China Wellcome, Trust Sanger Institute and Medical Research Council, UK.

Participating Centres

• Beijing Youan hospital, Capital Medical University, Beijing, China.
• MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford, UK.
• The Computational Biology Research Group, Weatherall Institute for Molecular Medicine, Oxford University, Oxford, UK.
• Chinese National Influenza Center, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.
• Oxford Centre for Respiratory Medicine, Q4 Oxford University Hospital NHS Trust, Headington OX3 7LH, UK.
• Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
• UCL/MRC Centre for Medical Molecular Virology, Research Department of Infection, Division of Infection and Immunity, University College London, Gower Street, London WC1E 6BT, UK.