Polymorphisms of COX-1 and GPVI associate with the antiplatelet effect of aspirin in coronary artery disease patients

被引:100
作者
Lepäntalo, A
Mikkelsson, J
Reséndiz, JC
Viiri, L
Backman, JT
Kankuri, E
Karhunen, PJ
Lassila, R
机构
[1] Univ Helsinki, Cent Hosp, Div Hematol, Dept Internal Med, FIN-00029 Helsinki, Finland
[2] Tampere Univ, Hosp & Med Sch, Lab Ctr, Res Unit, FIN-33101 Tampere, Finland
[3] Wihuri Res Inst, SF-00140 Helsinki, Finland
[4] Univ Helsinki, Dept Clin Pharmacol, FIN-00014 Helsinki, Finland
[5] Univ Helsinki, Inst Biomed, FIN-00014 Helsinki, Finland
关键词
aspirin; cyclo-oxygenase-1; genotype; glycoprotein VI; coronary artery disease;
D O I
10.1160/TH05-07-0516
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The antiplatelet effect of aspirin varies individually. This study evaluated whether the antiplatelet effect of aspirin associates with polymorphisms in the genes coding for cyclo-oxygenase-I (COX-I) and several platelet glycoprotein (GP) receptors in patients with stable coronary artery disease (CAD). Blood samples were collected from 101 aspirin-treated (mean 100 mg/d) patients. Compliance to treatment was assessed by plasma salicylate measurement. Platelet functions were assessed by two methods: 1) Response to arachidonic acid (AA, 1.5 mmol/L in aggregometry, and 2) PFA-100, evaluating platelet activation under high shear stress in the presence of collagen and epinephrine (CEPI). Aspirin non-response was defined as: 1) slope steeper than 12%/min in AA-aggregations, and 2) by closure time shorter than 170 s in PFA-100. The methods used detected different individuals as being aspirin non-responders. Five and 21 patients, respectively, were non-responders according tovAA-induced aggregation and PFA-100. Increased plasma thromboxane B-2 levels correlated with poor aspirin-response measured with both AA-induced aggregations and PFA-100 (P=0.02 and P=0.003, respectively). Of the non-responders detected by AA, 3 of 5 (60%) carried the rare G allele for the -A842G polymorphism of COX-I in contrast to 16 of 96 (17%) responders (P=0.016). Diabetes was associated with poor response. Aspirin non-response detected by PFA-100 associated with C13254T polymorphism of GP VI and female gender (P=0.012 and P=0.019, respectively). Although two patients were possibly non-compliant, this did not effect present conclusions. Evaluation of aspirin efficacy by AA-induced aggregation and PFA-100 detected different individuals, with different genotypic profiles, as being aspirin non-responders.
引用
收藏
页码:253 / 259
页数:7
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