Researchers from UC San Diego School of Medicine Department of Pediatrics joined an international research team, including colleagues from The University of Western Australia, the Genome Institute of Singapore, Emma Children's Hospital, The Netherlands, and Imperial College London, UK. The group studied naturally occurring genetic variation in almost 900 cases of Kawasaki disease from these countries. UC San Diego coordinated the U.S. genetics effort, collecting DNA samples from around the country.
"KD tends to run in families, suggesting that there are genetic components to disease risk," said Jane C. Burns, M.D., professor and Chief, Division of Allergy, Immunology, and Rheumatology, UC San Diego Department of Pediatrics. "We have been trying to understand the step by step development of this disease (pathogenesis) and the chain of events leading to it, using a biological approach but with limited success. This robust, systematic genome wide study is simply letting the genetics tell us what are the key genes in KD pathogenesis. Without this research these newly discovered genes of interest might have continued to remain hidden."
Kawasaki disease is an unusual and serious illness of young children that causes high fever, rash, red eyes and lips, swollen glands, and swollen hands and feet with peeling skin. The disease also causes damage of 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, but it seems to be due to an infection in susceptible children. There is no diagnostic test for Kawasaki disease, and current treatment fails to prevent coronary damage in at least one in 10-20 children and death in one in 1,000 children.
This study found that genes involved in cardiovascular function and inflammation may be particularly important and some seem to function together. The authors consider that these findings will lead to new diagnostics and better treatment and may be informative about adult cardiovascular disease as well.
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 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.
"So now it is time to come back to the biology and study the genes and the pathways and their role in KD pathogenesis," explained associate project scientist Chisato Shimizu, M.D., Kawasaki Disease Research Center, UC San Diego School of Medicine. "Most importantly, we will be able to use these data to help us predict which children with Kawasaki disease are at most risk for heart disease from their KD."
"Our laboratory is the focal point where the combination of academic research and clinical investigation lead to better treatment and patient outcome," explained Kawasaki Disease Research Center Assistant Director, Adriana Tremoulet, M.D., assistant adjunct professor, UC San Diego Department of Pediatrics and Rady Children's Hospital. "UC San Diego represents the entire U.S. genetics consortium. Through a grant from the NIH we have been able to support DNA collection in Los Angeles, Hawaii, Chicago, and Boston, as well as Japan and Finland. We coordinate the entire U.S. KD genetics effort and are the conduit for U.S. DNA to join the international effort based in Singapore."
Burns says the next steps include "drilling down" on candidate genes and pathways that were discovered in the genome-wide analysis. This detailed analysis will identify the exact genetic differences that influence disease susceptibility and outcome.
"We can already see a way in which this suggests a new treatment for KD that may be much less expensive than the current treatment with IVIG (intravenous immunoglobulin)," said Burns.
'Icebreaker' protein opens genome for t cell development, Penn researchers find
21.02.2018 | University of Pennsylvania School of Medicine
Similarities found in cancer initiation in kidney, liver, stomach, pancreas
21.02.2018 | Washington University School of Medicine
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.
But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...
Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.
The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...
Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters
Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
21.02.2018 | Life Sciences
21.02.2018 | Life Sciences
21.02.2018 | Materials Sciences