Cyclooxygenase-1 haplotype C50T/A-842G does not affect platelet response to aspirin.
COX-1 polymorphism C50T, in complete linkage disequilibrium with the other polymorphism A-842G, has been depicted as a determinant of pharmacological response to aspirin treatment. Whether these polymorphisms exert an effect on response to aspirin both in vitro and ex vivo is still controversial. We genotyped a population of 148 healthy individuals for the C50T/A-842G haplotype. Thirty of them underwent low-dose aspirin (100 mg daily) treatment for four weeks and were followed up for seven days after withdrawal. In this subgroup, we evaluated the thromboxane-dependence of biochemical and functional indexes used to monitor the antiplatelet effect of low-dose aspirin. Among the 148 subjects studied, 10 were heterozygous for the C50T/A-842G haplotype (6.7%) and only one was homozygous for the 50T/-842G haplotype (0.67%). In the group on low-dose aspirin, serum thromboxane (TX) B(2) as well as urinary 11-dehydro-TXB(2) and arachidonic acid (AA)-induced aggregation were similarly suppressed in carriers and non-carriers of the 50T/-842G haplotype, with an increase until basal levels of all the parameters within seven days after withdrawal. We found no relationship between the 50T/-842G haplotype and the so-called phenomenon of aspirin resistance. Platelet cyclooxygenase activity, as reflected by serum TXB(2), was uniformly and persistently suppressed by low-dose aspirin in both carriers and non carriers of these polymorphisms.
Center of Excellence on Aging, 'G. d'Annunzio' University Foundation, Chieti, Italy.
Caterina
C
Pettinella
Mario
M
Romano
Liborio
L
Stuppia
Francesca
F
Santilli
Rossella
R
Liani
Giovanni
G
Davì
D000284:Administration, Oral; D000328:Adult; D016718:Arachidonic Acid / Q000652:urine; D001241:Aspirin / Q000008:administration & dosage*; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D051545:Cyclooxygenase 1 / Q000235:genetics* / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007558:Italy; D008297:Male; D010641:Phenotype; D010974:Platelet Aggregation / Q000187:drug effects / Q000235:genetics; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000097:blood / Q000652:urine; D055815:Young Adult
D016861:Cyclooxygenase Inhibitors; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D001241:Aspirin