Navigation Links
International research collaboration narrows focus on genetic cause of Kawasaki disease
Date:12/17/2007

Researchers from Japans 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 childs 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.

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 Childrens 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 bodys 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 thats 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 persons 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.


'/>"/>

Contact: Kimberly Edwards
kedwards@ucsd.edu
619-543-6163
University of California - San Diego
Source:Eurekalert

Related medicine news :

1. International study strengthens case for daily calcium pill
2. Mettler-Toledo International Inc. Announces Webcast of Presentation at Thomas Weisel Partners 2007 Healthcare Conference
3. Australian-led international study shows blood pressure drugs cut death rate in type 2 diabetes
4. LCA Hails International Investigators Studying Lung Cancer
5. Arrow International Urges Shareholders To Vote for Approval of the $45.50 Teleflex Inc. Merger and for the Current Board of Directors
6. PRA International Adds Dr. Susan Stansfield as Executive Vice President
7. Medical Services International Maintains Pace in Second Quarter
8. Clarity Imaging International, Inc. Rolls Out Mobile DEXA Program
9. International Gateway Insurance Brokers Partners With MEDILINQ
10. Tulane University to receive $14M for international HIV/AIDS program
11. International Database Seeks to Boost Treatment of Altitude Sickness
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/24/2016)... ... ... crisis. Her son James, eight, was out of control. Prone to extreme mood shifts and ... him, he couldn’t control his emotions,” remembers Marcy. “If there was a knife on ... say he was going to kill them. If we were driving on the freeway, ...
(Date:6/24/2016)... ... ... Global law firm Greenberg Traurig, P.A. announced that 20 Florida attorneys are recognized ... this recognition are considered among the top 2 percent of lawyers practicing within the ... this year’s Legal Elite Hall of Fame: Miami Shareholders Mark D. Bloom, Burt ...
(Date:6/24/2016)... ... ... Comfort Keepers® of San Diego, CA is excited to announce they are ... drive cancer patients to and from their cancer treatments. Comfort Keepers provides quality ... and ongoing independence. Getting to and from medical treatments is one of the ...
(Date:6/24/2016)... ... June 24, 2016 , ... People across the U.S. are sharpening their pencils ... an essay contest in which patients and their families pay tribute to a genetic ... 2016 National Society of Genetic Counselors (NSGC) Annual Education Conference (AEC) this September. ...
(Date:6/24/2016)... ... June 24, 2016 , ... The Haute Beauty Network, affiliated ... Weintraub as a prominent plastic surgeon and the network’s newest partner. , ... most handsome men, look naturally attractive. Plastic surgery should be invisible.” He stands ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... VIEW, Calif. , June 23, 2016 ... a.m. CST on Thursday, July 7, 2016 , , , ... kayla.belcher@frost.com ) , , , , EXPERT PANELISTS:  , ... Nitin Naik; Senior Industry Analyst, Christi Bird; Senior Industry Analyst, Divyaa ... The global pharmaceutical industry is witnessing an ...
(Date:6/23/2016)... June 23, 2016  Guerbet announced today that it ... Supplier Horizon Award . One of 12 ... recognized for its support of Premier members through exceptional ... excellence, and commitment to lower costs. ... recognition of our outstanding customer service from Premier," says ...
(Date:6/23/2016)... YORK , June 23, 2016 ... waters, but it continues to present great opportunities to ... companies for today: Intrexon Corp. (NYSE: XON ... Arena Pharmaceuticals Inc. (NASDAQ: ARNA ), and ... more about these stocks and receive your complimentary trade ...
Breaking Medicine Technology: