Susceptibility genes for Kawasaki disease: toward implementation of personalized medicine

Kawasaki disease (KD) is an acute systemic vasculitis syndrome, which primarily affects in children under the age of 5 years. In 20–25% of cases, if untreated, coronary artery lesions develop, making KD the leading cause of acquired heart disease in children in both Japan and the United States. Since 1970, 19 nationwide surveys of KD in Japan have been conducted every 2 years and the data are stored in a database. Even though the etiology of KD remains unknown, despite enthusiastic research spanning more than 40 years, we have learnt a great deal about KD from this enormous database. These 19 epidemiologic studies indicate a strong genetic influence on the disease susceptibility, prompting us and other researchers to identify the responsible genes for KD by applying either the candidate gene approach or the genome-wide approach. We have employed a genome-wide linkage study using affected sibling pair data of KD in Japan and have identified several susceptibility loci. Further analysis focusing on a region of chromosome 19, where one of the linked loci was detected, identified a predisposing gene, which codes inositol 1,4,5-trisphosphate 3-kinase C (ITPKC). In this review, we summarize the cumulative knowledge regarding KD, and then outline our hypothesis of the role ITPKC plays in KD susceptibility and our trial that aims toward the implementation of personalized medicine for KD.