30 January 2013

Fighting against the flu

Genetic variant is associated with severe flu in the Chinese population

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

C allele at SNP 12252 associated with disease severity in acutely influenza A. [Doi: 10.1038/ncomms2433]


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," says Dr Tao Dong, Lead author from the MRC Human Immunology Unit, Oxford University. "We became interested in this because we noticed it is 100 times more common in China.

" Understanding why some people may be more severely affected by influenza than others is crucial in improving our ability to manage flu epidemics "

Professor Paul Kellam

"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."

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," says Professor Paul Kellam, co-author from the Wellcome Trust Sanger Institute. "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."

Notes to Editors

Publication details

  • Interferon-induced transmembrane protein-3 genetic variant rs12252-C is associated with severe influenza in Chinese individuals.

    Zhang YH, Zhao Y, Li N, Peng YC, Giannoulatou E, Jin RH, Yan HP, Wu H, Liu JH, Liu N, Wang DY, Shu YL, Ho LP, Kellam P, McMichael A and Dong T

    Nature communications 2013;4;1418


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.

Medical Research Council

Over the past century, the Medical Research Council has been at the forefront of scientific discovery to improve human health. Founded in 1913 to tackle tuberculosis, the MRC now invests taxpayers' money in some of the best medical research in the world across every area of health. Twenty-nine MRC-funded researchers have won Nobel prizes in a wide range of disciplines, and MRC scientists have been behind such diverse discoveries as vitamins, the structure of DNA and the link between smoking and cancer, as well as achievements such as pioneering the use of randomised controlled trials, the invention of MRI scanning, and the development of a group of antibodies used in the making of some of the most successful drugs ever developed. Today, MRC-funded scientists tackle some of the greatest health problems facing humanity in the 21st century, from the rising tide of chronic diseases associated with ageing to the threats posed by rapidly mutating micro-organisms.


MRC Centenary Timeline

The MRC Centenary Timeline chronicles 100 years of life-changing discoveries and shows how our research has had a lasting influence on healthcare and wellbeing in the UK and globally, right up to the present day.


Oxford University's Medical Sciences Division

Oxford University's Medical Sciences Division is one of the largest biomedical research centres in Europe, with over 2,500 people involved in research and more than 2,800 students. The University is rated the best in the world for medicine, and it is home to the UK's top-ranked medical school.

From the genetic and molecular basis of disease to the latest advances in neuroscience, Oxford is at the forefront of medical research. It has one of the largest clinical trial portfolios in the UK and great expertise in taking discoveries from the lab into the clinic. Partnerships with the local NHS Trusts enable patients to benefit from close links between medical research and healthcare delivery.

A great strength of Oxford medicine is its long-standing network of clinical research units in Asia and Africa, enabling world-leading research on the most pressing global health challenges such as malaria, TB, HIV/AIDS and flu. Oxford is also renowned for its large-scale studies which examine the role of factors such as smoking, alcohol and diet on cancer, heart disease and other conditions.

The Wellcome Trust Sanger Institute

The Wellcome Trust Sanger Institute is one of the world's leading genome centres. Through its ability to conduct research at scale, it is able to engage in bold and long-term exploratory projects that are designed to influence and empower medical science globally. Institute research findings, generated through its own research programmes and through its leading role in international consortia, are being used to develop new diagnostics and treatments for human disease.


The Wellcome Trust

The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. We support the brightest minds in biomedical research and the medical humanities. Our breadth of support includes public engagement, education and the application of research to improve health. We are independent of both political and commercial interests.


Contact the Press Office

Mark Thomson Senior Media and Public Relations Officer
Wellcome Trust Sanger Institute, Hinxton, Cambs, CB10 1SA, UK

Tel +44 (0)1223 492 384
Mobile +44 (0)7753 775 397
Fax +44 (0)1223 494 919
Email press.office@sanger.ac.uk

* quick link - http://q.sanger.ac.uk/pkzy2oqj