Momary Kathryn M, Shapiro Nancy L, Brace Larry D, Shord Stacy S, Grossi Enzo, Viana Marlos A, Helgason Cathy M, Nutescu Edith A, Cavallari Larisa H
Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, Ill., USA.
Cerebrovasc Dis. 2009;27(6):585-93. doi: 10.1159/000214223. Epub 2009 Apr 24.
We sought to determine whether cyclooxygenase-1 (PTGS1) genotype is associated with the ability of aspirin to inhibit platelet aggregation in patients at risk for stroke.
Blood and urine samples were collected from 60 subjects, including 28 African Americans, who were taking aspirin for primary or secondary stroke prevention. Samples were analyzed for the PTGS1 A-707G, PTGS1 P17L, and glycoprotein IIIa (ITGB3)P1(A1/A2) genotypes, ex-vivo platelet aggregation, serum cholesterol, plasma salicylate levels, and urinary 11-dehydrothromboxane B(2) (11-dhTxB(2)) concentrations. The association between PTGS1 A-707G and P17L genotypes and aspirin response, as assessed by ex vivo studies and 11-dhTxB(2) concentrations, was evaluated by statistical testing and nonlinear mapping.
Salicylate concentrations, ITGB3 genotype distribution and 11-dhTxB(2) concentrations were similar among PTGS1 genotype groups. More subjects with the PTGS1 17PP versus PL genotype had incomplete ex-vivo inhibition of platelet aggregation by aspirin (57 vs. 20%; p = 0.04). Fifty-nine percent of subjects homozygous for both the PTGS -707A and 17P alleles, but none with both the PTGS1 -707G and 17L alleles had incomplete inhibition with aspirin; p = 0.04. Similarly, nonlinear mapping showed a direct relationship between the PTGS1 17P allele and decreased aspirin response. When analyzed separately by ethnicity, the association with the P17L genotype and aspirin response persisted in African Americans, but not Caucasians.
Our data suggest that the PTGS1 P17L genotype contributes to response to aspirin as assessed by ex-vivo platelet aggregation. Our data further suggest that the association between PTGS1 genotype and aspirin response might vary by ethnicity.
我们试图确定环氧化酶-1（PTGS1）基因型是否与阿司匹林抑制中风高危患者血小板聚集的能力相关。
收集了60名受试者的血液和尿液样本，其中包括28名非裔美国人，这些受试者正在服用阿司匹林进行一级或二级中风预防。对样本进行PTGS1 A-707G、PTGS1 P17L和糖蛋白IIIa（ITGB3）P1（A1/A2）基因型分析、体外血小板聚集分析、血清胆固醇分析、血浆水杨酸水平分析以及尿11-脱氢血栓素B2（11-dhTxB2）浓度分析。通过统计学检验和非线性映射评估PTGS1 A-707G和P17L基因型与阿司匹林反应之间的关联，阿司匹林反应通过体外研究和11-dhTxB2浓度进行评估。
PTGS1基因型组之间的水杨酸浓度、ITGB3基因型分布和11-dhTxB2浓度相似。与PL基因型相比，更多PTGS1 17PP基因型的受试者在体外血小板聚集受到阿司匹林的不完全抑制（57%对20%；p = 0.04）。PTGS -707A和17P等位基因均为纯合子的受试者中有59%对阿司匹林的抑制不完全，但PTGS1 -707G和17L等位基因均有的受试者中无一例对阿司匹林的抑制不完全；p =
