Whole genome study reveals clues to solving the mystery behind Kawasaki disease

[theblackalchemist]

A study looking at the entire human genome has identified new genes that appear to be involved in making some children more susceptible to Kawasaki disease, according to a new international study published January 9 in the open-access journal PLoS Genetics. The research team, from The University of Western Australia, the Genome Institute of Singapore, Emma Children's Hospital, The Netherlands, Imperial College London, UK and the University of California San Diego, USA studied naturally occurring genetic variation in almost 900 cases of Kawasaki disease from these countries.

 

Kawasaki disease is an inflammatory condition in children that affects the mucus membranes, lymph nodes, walls of blood vessels, and the heart. Clinical signs include high fever, rash, and swollen hands and feet with skin peeling. Most importantly, the disease causes damage to the coronary arteries in a quarter of untreated children and may increase the risk of atherosclerosis in early adulthood. The cause of Kawasaki disease is unknown; an infectious etiology is suspected but not proven. There is no diagnostic test and current treatment fails to prevent coronary damage in at least 1 in 10 to 20 children. Kawasaki disease is fatal in approximately 1 in 1000 children.

 

This is the first genetic study of an infectious disease to examine the whole genome, rather than selected genes. The study shows that genes involved in cardiovascular function and inflammation may be particularly important and some seem to function together. The authors believe these findings could lead to new diagnostics and better treatment and may offer information about adult cardiovascular disease as well.

 

However, the findings do not yet prove that the new genes are functionally involved. Other genetic variants may be important, especially in different ethnic groups. The authors are now planning detailed studies of the function of these genes and larger collaborative studies including East Asian populations, who are at particular risk of Kawasaki disease, with 1 in 150 Japanese children affected.

 

 

 

Source: Public Library of Science

[theblackalchemist]

New genetic study sheds light on serious childhood disease

 

 

 

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.

 

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.

 

 

Source: Imperial College London

[theblackalchemist]

Since the above 2 articles are related, i made it into the same post.

TBA