title: Impact of genetic polymorphisms on platelet function and aspirin resistance.
abstract: 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.
authors.affiliation: Istanbul University, Istanbul Faculty of Medicine, Department of Cardiology, Turkey. bpamukcu@istanbul.edu.tr
authors.forename: Burak
authors.initials: B
authors.lastname: Pamukcu
authors.forename: Huseyin
authors.initials: H
authors.lastname: Oflaz
authors.forename: Imran
authors.initials: I
authors.lastname: Onur
authors.forename: Veysel
authors.initials: V
authors.lastname: Hancer
authors.forename: Selim
authors.initials: S
authors.lastname: Yavuz
authors.forename: Yilmaz
authors.initials: Y
authors.lastname: Nisanci
mesh_terms: 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
chemical_list: D001798:Blood Proteins; D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D003094:Collagen; D001241:Aspirin; D004837:Epinephrine