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

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

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