Abstract 13040: Combined Effects of Two Polymorphisms of the Alpha/beta Chain Genes of Fibrinogen in States of Advanced Atherosclerosis
Background: The association between fibrinogen and coronary artery disease (CAD) is well established. In addition, there are several genetic polymorphisms regulating fibrinogen levels and the risk of CAD. In the present study we investigated the effects of two common fibrinogen gene polymorphisms on coagulation/thrombosis and inflammatory process in patients with advanced atherosclerosis.
Methods: The study population consisted of 449 patients with CAD and 295 healthy individuals (controls), evaluated by coronary angiography or exercise test. The G455A (beta chain) and the G58A (alpha chain) polymorphisms were estimated by polymerase chain reaction (PCR) and the use of the HaeIII and the AciI restriction enzymes respectively. Serum levels of fibrinogen (mg/dl) were measured by the von Clauss method, plasminogen activity (%) was measured by standard coagulometry techniques, while soluble (s)CD40Ligand levels were measured by ELISA.
Results: The genotype distribution for the G58A was GG: 37.8%, GA: 39.4% and AA: 22.8% in CAD and GG: 33.5%, GA: 44.3% and AA: 22.2% in controls. In addition, the G455A genotype distribution was GG: 50.7%, GA: 41.5%, AA: 7.8% in CAD and GG: 54.5%, GA: 37.8%, AA: 7.7% in controls. We have shown that the G58A polymorphism had no significant effect on fibrinogen, sCD40L and plasminogen in both in controls and CAD (GG+GA vs AA, p=NS for all). On the contrary, 455AA homozygotes had significantly higher levels of fibrinogen (426.2±110.9 vs 368.8±92.9, p<0.05) as well as sCD40L (2.7±2.6 vs 1.2±1.0, p<0.05), but not plasminogen (p=NS) compared to G allele carriers in controls. Importantly, 455AA homozygotes revealed also higher levels of fibrinogen (539.9±132.7 vs 428.3±126.5, p<0.001) and plasminogen (118.7±15.8 vs 110.6±16.2, p<0.05), but not sCD40L (p=NS) compared to the G allele carriers in CAD patients.
Conclusions: Although the G58A polymorphism does not effect coagulation/thrombosis and inflammatory process, the G455A polymorphism alters significantly these processes. More specifically, the 455AA homozygosity is responsible for these effects and especially through the striking effect on fibrinogen levels both in patients and healthy individuals.
- © 2011 by American Heart Association, Inc.