Pettinella Caterina, Romano Mario, Stuppia Liborio, Santilli Francesca, Liani Rossella, Davì Giovanni
Center of Excellence on Aging, 'G. d'Annunzio' University Foundation, Chieti, Italy.
Thromb Haemost. 2009 Apr;101(4):687-90.
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.
COX - 1基因多态性C50T与另一多态性A - 842G处于完全连锁不平衡状态，已被描述为阿司匹林治疗药理反应的一个决定因素。这些多态性是否在体外和体内对阿司匹林反应产生影响仍存在争议。我们对148名健康个体的C50T/A - 842G单倍型进行了基因分型。其中30人接受了低剂量阿司匹林（每日100毫克）治疗四周，并在停药后随访七天。在这个亚组中，我们评估了用于监测低剂量阿司匹林抗血小板作用的生化和功能指标对血栓素的依赖性。在研究的148名受试者中，10人是C50T/A - 842G单倍型的杂合子（6.7%），只有1人是50T/- 842G单倍型的纯合子（0.67%）。在低剂量阿司匹林组中，50T/- 842G单倍型的携带者和非携带者的血清血栓素（TX）B2以及尿11 - 脱氢 - TXB2和花生四烯酸（AA）诱导的聚集受到类似抑制，停药后七天内所有参数均回升至基础水平。我们发现50T/- 842G单倍型与所谓的阿司匹林抵抗现象之间没有关系。血清TXB2反映的血小板环氧化酶活性在这些多态性的携带者和非携带者中均被低剂量阿司匹林持续且一致地抑制。
