Objectif
Thrombotic stroke is a disabling condition - affecting an estimated 650,000 Europeans annually, with considerable mortality and costing over ¬30 billion/yr. Genetic factors account for a substantial component of the incidence & mortality of stroke. There is little effective therapy. EUROCLOT aims to identify and validate potentially therapeutically useful genes associated with thrombotic stroke using a novel approach. Stroke is a complex end-point disease involving the interaction of many pathologic processes, such as vessel wall atheroma, hypertension, platelet function & coagulation. EUROCLOT focuses on uncovering the genes that control the end-stage of the coagulation process that leads directly to the production of the thrombus (clot) that causes vascular obstruction and tissue death. Clinical studies indicate that alterations in fibrin structure and/or function create a prothrombotic phenotype which increases vascular risk. Twin studies have shown a substantial genetic component to levels of activation peptides and the final common pathway of thrombus (fibrin structure/function). We aim specifically to identify the major genes involved in variations of the end-stage clotting process and investigate the role of these novel genes (and existing candidate genes) in the pathogenesis of stroke across Europe. EUROCLOT will study stroke intermediate phenotypes in 4500 twins from GenomEUtwin project involving 8 countries and 1000 subjects from extended families from the GAIT2 (Spain) and EuroHead (Finland) studies. Genes will be validated in 1500 stroke cases including those from the large European prospective MORGAM study. Cross-European differences in allelic frequencies will be examined along with their relative impacts. Phenotyping will be standardised and harmonised and a European database established. Close links with European SMEs will ensure that all findings from EUROCLOT are maximally exploited to develop future novel diagnostics and therapeutic targets.
Champ scientifique
Appel à propositions
FP6-2003-LIFESCIHEALTH-I
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Régime de financement
STREP - Specific Targeted Research ProjectCoordinateur
LONDON
Royaume-Uni