Genetic Determinants of Arterial Thrombosis

Abstract

Abstract-Arterial thrombosis is a complex disorder that involves multiple genetic and environmental factors interacting to produce the characteristic phenotype. In the past decades, investigators have focused on the molecular genetics of arterial vascular disorders and have identified numerous polymorphisms and mutations in genes related to the hemostatic system and to enzymes involved in the synthesis and bioavailability of nitric oxide (NO); however, the relation between most polymorphisms and the risk of coronary artery disease, ischemic stroke, and peripheral vascular disease remains highly controversial. In this review, we describe the most common genetic variations involved in the pathogenesis of arterial thrombosis, their functional implications, and their association with disease risk. Specifically, we consider polymorphisms in coagulation factors (fibrinogen, prothrombin, FV Leiden, FVII, and FXIII); fibrinolytic factors (tissue-type plasminogen activator, plasminogen activator inhibitor-1, and thrombin-activatable fibrinolysis inhibitor); platelet surface receptors; methylenetetrahydrofolate reductase; endothelial NO synthase; and the antioxidant enzymes paraoxonase and plasma glutathione peroxidase. Overall, there seems to be a modest contribution of individual genetic variants in the hemostatic and antioxidant systems to the risk of arterial thrombosis. Thus, future research ought to focus on identifying novel genetic determinants and on the interaction of these genetic risk factors with each other and the environment to understand better the pathobiology and susceptibility to arterial thrombotic disease.

Frontiers in Nephrology

“…Examples of genomic, proteomic, and metabolomic attempts to classify and diagnose vascular diseases already exist. [23][24][25] This tortuous path urgently needs to be taken.…”

Atherothrombotic Disorders

“…8 Available data suggest that a single genetic susceptibility factor may have an important impact on the occurrence of arterial thrombosis only when combined with other genetic and/or acquired risk factors. 11,14,19 On the other hand, there is also evidence that inherited thrombophilic states play a significant role precisely among patients with a low a priori cardiovascular risk profile (eg, young, female, without traditional cardiovascular risk factors). In these cases, it is conceivable that as yet unrecognized or poorly appreciated genetic and/or acquired/environmental conditions interact with the known inherited variants to promote arterial thrombosis.…”

Genetic Risk Factors for Arterial Thrombosis and Inflammation

“…Though several small studies have suggested a role in select populations, particularly in children and in young women with myocardial infarction, 2,3 no effect has been seen in a number of larger studies, 4 including the Physicians' Health Study. 5 The general conclusion has been that these common genetic variants are not major risk factors for myocardial infarction, stroke, or any other form of arterial thrombosis.…”