Genetic basis of human vascular and inflammatory diseases

?he present project aims to investigate genetic basis of systemic and vascular inflammation in chronic human inflammatory diseases: carotid atherosclerosis, multiple sclerosis, renal interstitial fibrosis and chronic ear inflammation, in parallel. To determine genetic markers as indicators of disease onset and end stage tissue damage, we will focus on genes coding molecules involved in innate immune response, chemokines/chemokine receptors, renin-angiotensin system and enzymes involved in extracellular matrix remodeling. The case-control design will be applied for investigation of candidate genes. The candidate gene expression will be investigated in human target tissues (atherosclerotic plaque, blood, CSF, urine, kidney and urinary tract tissue). Expression levels of miRNAs, new class of sequence-specific regulators of gene expression, will be investigated from total blood samples and target tissue. The SNPs identification, the gene expression quantification, on both RNA and protein level, the correlation of SNP with gene expression will be investigated in regard to disease susceptibility and progression. The comparison of systemic gene expression and local target tissue gene expression will be performed in aim to determine systemic biomarkers of tissue damage. The results of the project will be the identification of useful genetic biomarkers for diagnosis eg. susceptibility, prognosis eg. progression or even etiology of a human chronic inflammatory disease.