Identification of Disease-associated Genes for Cardiovascular Diseases

点击翻译按钮获取中文摘要

Myocardial infarction: We found significant associations of myocardial infarction with polymorphisms in SELE, PECAM1 and CD14. It also was revealed that the disease-associated SELE allele lead higher binding between leukocytes and vascular endothelial cells. In contrast no association was found for the reported polymorphisms in LTA, LGALS2 and p22phox genes via the analysis of more than 500 patients and 500 controls. On the other hand, we could identify five novel disease-related loci for myocardial infarction via the analysis of 18,800 microsatellite markers.Cardiomyopathy: Gene-Chip analysis of hypertrophied hearts and failing hearts from Dahl salt-sensitive hypertensive rats enabled us to identify 258 genes showing increased or decreased expression in association with hypertensive cardiomyopathy. By analyzing human orthologues of these genes we identified a BMP10 variant associated with hypertensive dilated cardiomyopathy. Biochemical and cell biological analyses revealed that BMP10 … More localized in Z-disc and bound Tcap. The BMP10 variant reduced the binding to Tcap and augmented extracellular secretion of BMP10. In addition, candidate gene approaches have revealed two novel disease genes for hypertrophic cardiomyopathy and four disease genes for dilated cardiomyopathy.Arrhythmia: In this study, we have identified many disease-associated mutations in cardiac channel genes and revealed functional changes caused by the mutations. In addition, an HCN4 mutation was revealed to be a novel disease gene for ventricular arrhythmia since a disease-linked mutation showed dominant loss-of-function of HCN4 channel.Vasculitis: We have investigated polymorphisms of microsatellite markers and SNPs in the HLA region in patients with Takayasu arteritis or Buerger disease. It was revealed that there were two disease-associated loci for Takayasu arteritis; one was HLA-B and the other was mapped in TNF-MICA region. In contrast, there were at least three disease-associated loci for Buerger disease; first was HLA-DPB1, second was HLA-DRB1, and third was mapped near the HLA-E gene. Less