Fibrinogen: A Circulating Factor in Search for Its Genetic Architecture
Fibrinogen (Coagulation factor I) is a major player in thrombus formation; it is cleaved by thrombin to form fibrin, which is the most abundant component of a blood clot1. Beyond the role played in the coagulation and cardiovascular diseases (CVD), fibrinogen is a proinflammatory factor in autoimmune and inflammatory diseases (such as rheumatoid arthritis, vasculitides, inflammatory bowel disease, multiple sclerosis, chronic obstructive pulmonary diseases and kidney disorders and post-transplant-fibrosis)2 as well as in several types of cancer3. Fibrinogen has been demonstrated to interfere with the immuno-inflammatory responses through binding to inflammatory cells via ligand-receptor interactions that are different from those involved in the coagulation cascade2. Fibrinogen also stimulates angioneogenesis in vitro and in vivo4 and acts as a mitogen for fibroblasts5. Therefore, fibrinogen is a multifaceted molecule that plays various roles in several human diseases.
Since family studies have demonstrated a major genetic component to variance of fibrinogen (44%)6, and increased levels of fibrinogen have been proved to be a marker of risk for cardiovascular diseases, the elucidation of the genetic architecture of plasma fibrinogen levels is becoming a major undertaking in translational research and an emerging clinical need.
- Received August 12, 2013.
- Accepted August 14, 2013.