Impact of genetic polymorphisms on platelet function and aspirin resistance.
Genetic polymorphisms may affect platelets' responses to the antiplatelet therapy. Our aim was to determine the role of genetic polymorphisms on aspirin resistance in patients with coronary heart disease (CHD). A total of 126 consecutive patients (35-85 years old, 32% women) with chronic stable CHD was enrolled in the study. Platelet function assays were realized by the platelet function analyzer (PFA)-100 with collagen and epinephrine (Col/Epi) and collagen and adenosine diphosphate (Col/ADP) cartridges. Aspirin resistance was defined as having a closure time of less than 186 s with Col/Epi cartridges despite regular aspirin therapy. Factor V, prothrombin, factor XIII, beta-fibrinogen, plasminogen activator inhibitor I (PAI-1), glycoprotein IIIa, methylene tetrahydrofolate reductase, ACE and ApoB gene polymorphisms were determined by three consecutive steps: isolation and amplification of DNA and reverse hybridization. We determined that 30 patients (23.8%) had aspirin resistance by the PFA-100. Mean closure time measured with the Col/ADP cartridges was 74 +/- 12 s (51-104 s). Ten of the 30 patients with aspirin resistance were women (33.3%). Genetic polymorphisms were determined in 30 aspirin-resistant and 17 aspirin-sensitive patients. No statistically significant relationship was determined between aspirin resistance and the genetic panel. In our study we did not determine a significant relationship between the aspirin resistance and factor V, prothrombin, factor XIII, beta-fibrinogen, PAI-1, glycoprotein IIIa, methylene tetrahydrofolate reductase, ACE and ApoB gene polymorphisms.
Pamukcu
Burak
B
Istanbul University, Istanbul Faculty of Medicine, Department of Cardiology, Turkey. bpamukcu@istanbul.edu.tr
Oflaz
Huseyin
H
Onur
Imran
I
Hancer
Veysel
V
Yavuz
Selim
S
Nisanci
Yilmaz
Y
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000368:Aged; D001241:Aspirin / Q000494:pharmacology* / Q000627:therapeutic use; D001798:Blood Proteins / Q000235:genetics*; D003094:Collagen / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics*; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects / Q000235:genetics*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D010979:Platelet Function Tests / Q000295:instrumentation; D011110:Polymorphism, Genetic; D019851:Thrombophilia / Q000097:blood / Q000188:drug therapy
D001798:Blood Proteins; D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D003094:Collagen; D001241:Aspirin; D004837:Epinephrine