title: Identification of susceptibility genes for Kawasaki disease.
abstract: Kawasaki disease is an acute febrile illness of infants and children with unknown etiology. Coronary artery lesions occurring in 20-25% of untreated patients of KD has made KD a leading cause of acquired heart diseases of childhood in developed countries. High prevalence in East Asian countries is one of the epidemiological features of KD and has suggested genetic factors underlying the disease pathogenesis. We tried to identify genetic variants relevant to KD susceptibility by sibpair linkage study and linkage diseuilibrium mapping with SNPs and found that inositol 1,4,5-trisphosphate 3-kianse C gene is a susceptibility gene for KD. We also found the negative regulatory role of ITPKC in TCR signaling and the mechanism by which the responsible SNP in intron 1 of the gene affects transcripts level of ITPKC. Our findings highlighted the importance of Ca(2+)/NFAT pathway in the pathogenesis of KD and shed light on the possibility of immuno-suppressants targeting the pathway as a therapeutic strategy for KD.
authors.affiliation: Laboratory for Cardiovascular disease, Center for Genomic Medicine, RIKEN.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Onouchi
mesh_terms: D002118:Calcium / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D007223:Infant; D015810:Linkage Disequilibrium; D009080:Mucocutaneous Lymph Node Syndrome / Q000235:genetics*; D050778:NFATC Transcription Factors / Q000502:physiology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics* / Q000502:physiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D006680:HLA Antigens; D050778:NFATC Transcription Factors; D011948:Receptors, Antigen, T-Cell; D017853:Phosphotransferases (Alcohol Group Acceptor); C051038:Inositol 1,4,5-trisphosphate 3-kinase; D002118:Calcium