New genetic study sheds light on serious childhood disease

Genetic variations that predispose children to Kawasaki Disease discovered - News Release

Imperial College London News Release

Under strict embargo for
01.00 GMT
Friday 9 January 2009

Genetic variations that can predispose children to a serious disease that damages the heart have been identified in a genome-wide association study of Kawasaki Disease, published today in PLoS Genetics.

The disease, the cause of which is currently unknown, is a rare and severe childhood disorder that occurs mainly in young children. It is the most common cause of childhood acquired heart disease in developed countries.

The disease is more common in Japanese children and those of Asian descent, but it is found in all ethnic groups, affecting around 1 in 10,000 children of Caucasian descent.

The new study identifies variations in 31 genes which appear to increase a child’s risk of developing Kawasaki Disease.

The findings will enable scientists to develop more effective ways of tackling the disease, by revealing new targets for treatment, say the researchers, from Imperial College London, the University of Western Australia, the Genome Institute of Singapore, Emma Childrens Hospital, Netherlands, and the University of San Diego California.

Some of the variations identified appear in genes that work together to control signalling between immune cells and heart cells. The researchers are planning to carry out further work to understand how these mutations contribute to the disease.

Epidemiological studies suggest that Kawasaki Disease is triggered by an as yet unidentified infection. It is currently treated using pooled antibodies from healthy donors. This treatment shortens the period of illness and most children recover after two to three weeks. It reduces but does not eliminate the risk of heart disease.

Kawasaki Disease can damage the heart

Professor Michael Levin, one of the authors of the study from the Department of Paediatrics at Imperial College London said: “Sadly, all the hospitals in the UK frequently see children with Kawasaki Disease. A child whose coronary arteries are damaged in early childhood faces a lifetime of uncertainty and risk, and we desperately need better treatments to prevent long term heart problems in those affected. We hope our new study will help us to reach this goal.”

Dr Victoria Wright, another author of the study from the Department of Paediatrics at Imperial College London said: “Kawasaki Disease was identified less than fifty years ago so it is a relatively new disease. We still have a long way to go with this research but this is an important step in understanding the disease better.”

For the new study, the international consortium combined their patients to perform a genome-wide association study in 119 Caucasian KD cases and 135 matched controls from Australia, Holland, USA and the UK. They looked at 250000 genetic variants in each patient and uncovered the most significant genes that appeared to be involved in Kawasaki Disease. They then replicated this in an independent cohort of a total of 893 KD cases plus population and family controls.

The researchers are now planning to analyse an Asian cohort of people with Kawasaki Disease, to see if their results can be replicated in this population.

-ENDS-

For further information please contact:

Lucy Goodchild
Press Officer
Imperial College London
e-mail: lucy.goodchild@imperial.ac.uk
Telephone: +44 (0)207 594 6702 or ext. 46702
Out of hours duty Press Officer: +44 (0)7803 886 248

Notes to editors:

1. About Kawasaki Disease

* Symptoms include prolonged fever, swollen glands, red eyes and lips, inflammation of the mouth, extensive rash, swollen and red hands and feet. Characteristically peeling of the skin on fingers and toes occurs during convalescence.

* Coronary arteries are damaged in up to 25% of untreated children, which can lead to coronary heart disease and in occasional cases (1%) to fatal heart attack.

2. "A Genome-Wide Association Study Identifies Novel And Functionally Related Susceptibility Loci For Kawasaki Disease" PLoS Genetics, 9 January 2009

Corresponding author: David Burgner, University of Western Australia (For a full list of authors please see paper.)

3. About Imperial College London

Consistently rated amongst the world's best universities, Imperial College London is a science-based institution with a reputation for excellence in teaching and research that attracts 12,000 students and 6,000 staff of the highest international quality. Innovative research at the College explores the interface between science, medicine, engineering and business, delivering practical solutions that improve quality of life and the environment - underpinned by a dynamic enterprise culture.

Since its foundation in 1907, Imperial's contributions to society have included the discovery of penicillin, the development of holography and the foundations of fibre optics. This commitment to the application of research for the benefit of all continues today, with current focuses including interdisciplinary collaborations to improve health in the UK and globally, tackle climate change and develop clean and sustainable sources of energy. Website:www.imperial.ac.uk