Featured Research

from universities, journals, and other organizations

New Genetic Variation That Affects A Child's Risk Of Getting Kawasaki Disease Discovered

Date:
December 19, 2007
Source:
University of California - San Diego
Summary:
Researchers have discovered a new genetic variation that affects a child's risk of getting Kawasaki disease, an illness characterized by acute inflammation of the arteries throughout the body. If untreated, KD can lead to lethal coronary artery aneurysms.

Researchers from Japan's RIKEN SNP Research Center, collaborating with a team at the University of California, San Diego (UCSD), have discovered a new genetic variation that affects a child's risk of getting Kawasaki disease (KD), an illness characterized by acute inflammation of the arteries throughout the body. The genetic variation influences immune activation and the response to standard treatment, as well as the risk of developing coronary artery aneurysms -- a swelling of the artery that can result in blood clots and heart attack -- as a complication of KD.

Related Articles


Lead author, Yoshi Onouchi, M.D., Ph.D., SNP Research Center, RIKEN, Yokohama, Japan, used DNA from hundreds of U.S. children and their parents, collected through the Kawasaki Disease Research Center at Rady Children's Hospital San Diego (RCHSD), Department of Pediatrics, UCSD School of Medicine.

"This was a wonderful collaboration," said co-author, Jane Burns, M.D., professor and chief, Division of Allergy, Immunology, and Rheumatology, UCSD Department of Pediatrics. "Dr. Onouchi used our DNA to make this observation. Now we are building on that observation."

Kawasaki Disease, a pediatric illness characterized by fever and rash, is not a rare illness but it is most prevalent in Japan. In San Diego County, 20 to 30 children per 100,000 children less than five years of age are affected each year. More than 50 new patients are treated annually at RCHSD. The illness is four to five times more common than some more publicly recognized diseases of children such as tuberculosis or bacterial meningitis.

If untreated, KD can lead to lethal coronary artery aneurysms. KD tends to run in families, suggesting that there are genetic components to disease risk. It is also 10 to 20 times more common in Japanese and Japanese American children than in children of European descent.

Researchers identified a region on chromosome 19 linked with the disease. In particular, a series of variants across four genes in the region appeared more frequently in individuals with the disease than those in the healthy control group.

The team focused on one of these genes, ITPKC, which appeared to be the most likely candidate. The gene lies in a signaling pathway that affects the activation of T cells, one arm of the body's immune response system. ITPKC encodes an enzyme that is part of a signaling pathway with a critical role in T cell activation. The authors showed that one of the risk variants reduces the expression of ITPKC, and that lower levels of ITPKC lead to over-activation of T cells.

"This single gene jumped out as an obvious candidate because it is involved in immune activation, and KD is a disease of immune over-activation," said Burns. "This was great detective work to decipher the function of this variant."

Study authors suggest that the association of ITPKC with Kawasaki disease may have immediate clinical implications. Up to 20% of children who have KD are resistant to the standard treatment with intravenous immunoglobulin. This therapy is more likely to fail in individuals with the ITPKC risk variant. If these individuals could be identified with a genetic test, they could be offered alternative, more intensive therapies.

Further studies will identify additional sites of genetic variation and may capture enough of the genetic influence that a diagnostic test can be devised to identify children at increased risk. These children with KD would be candidates for more aggressive therapy.

"A significant number of KD patients suffer irreversible coronary artery damage, which can lead to heart attack, heart failure, or require transplant," noted Burns. "Our goal at RCHSD is to create a genetic test for KD patients that will indicate whether the patient is at increased risk. If that's the case, we can use additional treatments and potentially reduce future complications."

In addition, the finding may have implications for understanding the genetic thermostat that regulates the intensity of a person's immune response to inflammation. Investigators are now looking at what impact this genetic variation might have on initiating other inflammatory conditions, such as atherosclerosis and myocarditis, an inflammation of the heart muscle often caused by a viral infection.

The Kawasaki Disease Research Program is a joint collaboration between the Departments of Pediatrics and Sociology at University of California, San Diego (UCSD), the Climate Center at Scripps Institution of Oceanography, and Rady Children's Hospital San Diego. The Program was created to help foster excellence in care for patients with Kawasaki Disease (KD) and to support clinical, laboratory, and epidemiologic investigation into the etiology, pathophysiology, and natural history of the disease. The program brings together investigators from more than 15 countries with diverse research interests and expertise to work together to further our understanding of this enigmatic disease.

Kawasaki Disease is often accompanied by the following symptoms: high fever and irritability; rash; swelling and redness of the hands and feet; bloodshot eyes; red mouth, lips, and throat; and swollen lymph nodes in the neck. It affects children almost exclusively; most patients are under 5 years of age. For reasons still unknown, males acquire the illness almost twice as often as females.


Story Source:

The above story is based on materials provided by University of California - San Diego. Note: Materials may be edited for content and length.


Cite This Page:

University of California - San Diego. "New Genetic Variation That Affects A Child's Risk Of Getting Kawasaki Disease Discovered." ScienceDaily. ScienceDaily, 19 December 2007. <www.sciencedaily.com/releases/2007/12/071216155440.htm>.
University of California - San Diego. (2007, December 19). New Genetic Variation That Affects A Child's Risk Of Getting Kawasaki Disease Discovered. ScienceDaily. Retrieved December 19, 2014 from www.sciencedaily.com/releases/2007/12/071216155440.htm
University of California - San Diego. "New Genetic Variation That Affects A Child's Risk Of Getting Kawasaki Disease Discovered." ScienceDaily. www.sciencedaily.com/releases/2007/12/071216155440.htm (accessed December 19, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, December 19, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Best Tips to Curb Holiday Carbs

The Best Tips to Curb Holiday Carbs

Buzz60 (Dec. 19, 2014) It's hard to resist those delicious but fattening carbs we all crave during the winter months, but there are some ways to stay satisfied without consuming the extra calories. Vanessa Freeman (@VanessaFreeTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Sierra Leone Bikers Spread the Message to Fight Ebola

Sierra Leone Bikers Spread the Message to Fight Ebola

AFP (Dec. 19, 2014) More than 100 motorcyclists hit the road to spread awareness messages about Ebola. Nearly 7,000 people have now died from the virus, almost all of them in west Africa, according to the World Health Organization. Video provided by AFP
Powered by NewsLook.com
Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Buzz60 (Dec. 19, 2014) A double-amputee makes history by becoming the first person to wear and operate two prosthetic arms using only his mind. Jen Markham has the story. Video provided by Buzz60
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins