Genetic risk factors of atherothrombosis.

Atherothrombosis is a preventable and multifaceted pathological disorder, whose pathogenesis involves a large number of biological pathways such as lipid and hormonal metabolism, inflammation and hemostasis. Although it has been known for a long time that atherosclerosis has a sizable hereditary component, research on the field of genetics of cardiovascular disease is still ongoing, with doubts often outweighing certainties. The large amount of evidence gathered so far allows to identify at least five potential important pathways that can be specifically targeted by genetic studies, which include lipoprotein metabolism, inflammation, the renin-angiotensin-aldosterone system, platelet function, blood coagulation and fibrinolysis. Due to the large number of published studies that have investigated the role of genetic polymorphisms in the pathogenesis of atherothrombosis and its complications, we have focused this review on data emerging from meta-analyses. The available evidence suggests that some selected polymorphisms in low density lipoprotein (LDL) metabolism, C reactive protein (CRP) and blood coagulation (especially Factor V Leiden, prothrombin G20210A polymorphism and plasminogen activator inhibitor-1) are those that deserve major focus. It is also noteworthy, however, that it seems very implausible that one single polymorphism will add much to the current approach of risk assessment based on conventional risk factors. A paradigm shift would hence be needed in the current approach to genetics of atherothrombosis, wherein investigation of entire pathways rather than assessment of isolate mutations will likely provide more useful information for complex conditions that involve large numbers of genes and are subjected to environmental regulation of gene expression and cellular phenotype