Genetic risk factor of venous thromboembolism and its recurrence

VTE is the third most common cardiovascular disease. The most severe manifestation is fatal pulmonary embolism. Ten 10% of the population have been affected by the age of 80 years. VTE is caused by a complex interaction of genetic and acquired risk factors, and may under certain condition affect young people also. Treatment is efficient but at the price of severe or even fatal bleeding. Therefore there is a need for risk assessment to identify those who will benefit most from treatment. Genetic and clinical risk factors have been used to stratify patients however, in a large proportion of patients no acquired or genetic risk factor is found even in those with family history of VTE. Furthermore, microRNAs which are small non-coding RNA molecules are stably present in a range of body fluids and have recently been shown to be useful biomarkers in many diseases. However, their role in VTE is unknown.

In this project we will study potential novel factors in the form of microRNA and genetic variants. This will be done using agnostic methods like arrays of approximately 750 circulating microRNA in plasma and latest next generation sequence technique. We will use samples from three well defined cohorts in order to identify and validate diagnostic and predictive values of newly identified genetic variants and miRNAs.
This will be the first study of its kind in VTE and the intention is not only to identify novel biomarkers and novel genetic variants associated with VTE but also to better understand which molecular pathways involved in VTE. Thus, the study may both result in better risk assessment and treatment of VTE and elucidation of the pathogenesis of VTE, which may create new therapeutic strategies for treatment for VTE with fewer side effects. If the successful the results will be of importance not only for risk assessment and treatment in clinical practice but also for development of novel therapeutic agents.