Genetic polymorphisms and atrial fibrillation: Insights into the prothrombotic state and thromboembolic risk.
The pathophysiology of thromboembolism in atrial fibrillation (AF) is a multifactorial and complex process. Abnormalities of haemostasis, fibrinolysis, endothelium, and platelets have all been described in AF. This prothrombotic state observed in AF appears to be additive to the presence of clinical and echocardiography risk factors for thromboembolism. Nonetheless, the precise mechanistic pathway(s) leading to the prothrombotic state in AF remain to be elucidated. Of note, there are limited data on the influence of genetic polymorphisms in thromboembolic risk associated with AF. On the other hand, the response to coumarin derivatives depends on several factors, such as sex, age, diet, or interacting drugs. Optimal anticoagulation control is usually hampered by significant interindividual variability in dose requirements for a given target level of anticoagulation. There is increasing evidence that interindividual sensitivity and side-effects to coumarinics may be largely determined genetically. Thus, genetic polymorphisms could explain the individual risk of developing an adverse drug reaction (bleeding) or drug inefficacy (thrombosis) with oral anticoagulation. In this article, we provide an overview of the limited data about the possible influence of genetic polymorphisms on thromboembolic risk in AF, as well as the genetic influences on anticoagulant drug responsiveness.
López-Cuenca
Angel
A
Department of Cardiology, Hospital Universitario Virgen Arrixaca, Murcia, Spain.
Marín
Francisco
F
Roldán
Vanessa
V
González-Conejero
Rocío
R
Hernández-Romero
Diana
D
Valdés
Mariano
M
Lip
Gregory Y H
GY
D001281:Atrial Fibrillation / Q000150:complications*; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000235:genetics*; D013923:Thromboembolism / Q000453:epidemiology / Q000235:genetics*; D019851:Thrombophilia / Q000453:epidemiology / Q000235:genetics*