Abstract for presentation at 11th International Congress of Human Genetics

Tissue Inhibitor of Metalloproteinase 2 and Chemokine, CC Motif, Ligand 3 are Novel Molecular Markers to Predict the Development of Coronary Artery Lesions in Kawasaki Disease

  • Dr Kenji Furuno, Kyushu University, Japan
  • Dr Hidetoshi Takada, Kyushu University, Japan
  • Dr Ken Yamamoto, Medical Institute of Bioregulation, Kyushu University, Japan
  • Dr Kazuyuki Ikeda, Kyushu University, Japan
  • Dr Takuro Ohno, Kyushu University, Japan
  • Dr Yumi Mizuno, Fukuoka Children's Hospital and Medical Center for Infectious Diseases, Japan
  • Dr Toshiro Hara, Kyushu University, Japan

    • Background: Kawasaki disease (KD) is an acute febrile vasculitis and the most common cause of acquired cardiac disease in children. In spite of numerous studies on KD, its etiology and pathogenesis remain unclear. Several scoring systems and cytokines have been reported to be possible markers to predict the development of coronary abnormalities. However, the precise prediction of the CAL risk has not yet been established.
    Objective: To identify cytokine genes uniquely expressed in peripheral blood mononuclear cells (PBMNCs) in the acute phase of Kawasaki disease (KD) with coronary artery lesions (CAL).
    Methods: We compared the mRNA expression levels of PBMNCs from four KD patients with and without CAL by the DNA microarray. The genes that showed unique expressions in KD with CAL were further quantitated for the mRNA expression levels by real-time PCR. The genetic association study was performed to analyze the significance of single nucleotide polymorphisms in these genes for the development of CAL in KD patients.
    Results: The microarray analysis showed that Tissue Inhibitor of Metalloproteinases 2 (TIMP2) and chemokine, CC motif, ligand 3 (CCL3) genes were expressed at significantly higher levels in PBMNCs of KD with CAL than in those without CAL. The quantitative real-time RT-PCR confirmed that the expression levels of these genes were significantly higher in KD patients with CAL than in those without CAL (p<0.05), although no laboratory data on admission showed significant difference between the two groups. Among KD patients, TIMP2 promoter polymorphisms were significantly associated with a risk of CAL (p<0.01). There was a significant difference in the transcriptional activities between the haplotypes of the TIMP2 promoter polymorphisms by reporter assay using U-937 cells.
    Conclusion: TIMP2 and CCL3 gene expression levels and TIMP2 promoter polymorphisms might be used as the early predictors of coronary lesions in KD.

    Conference Organiser - ICMS Pty Ltd