Supplementary Material for: Influence of Cyclooxygenase-1 Genotype on ex vivo Aspirin Response in Patients at Risk for Stroke

<i>Background:</i> We sought to determine whether cyclooxygenase-1 <i>(PTGS1)</i> genotype is associated with the ability of aspirin to inhibit platelet aggregation in patients at risk for stroke. <i>Methods:</i> 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 <i>PTGS1 </i>A–707G, <i>PTGS1</i> P17L, and glycoprotein IIIa (<i>ITGB3</i>)P1<sup>A1/A2</sup> genotypes, ex-vivo platelet aggregation, serum cholesterol, plasma salicylate levels, and urinary 11-dehydrothromboxane B<sub>2</sub> (11-dhTxB<sub>2</sub>) concentrations. The association between <i>PTGS1 </i>A–707G and P17L genotypes and aspirin response, as assessed by ex vivo studies and 11-dhTxB<sub>2</sub> concentrations, was evaluated by statistical testing and nonlinear mapping. <i>Results:</i> Salicylate concentrations, <i>ITGB3</i> genotype distribution and 11-dhTxB<sub>2</sub> concentrations were similar among <i>PTGS1</i> genotype groups. More subjects with the <i>PTGS1 </i>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 <i>PTGS</i> –707A and 17P alleles, but none with both the <i>PTGS1</i> –707G and 17L alleles had incomplete inhibition with aspirin; p = 0.04. Similarly, nonlinear mapping showed a direct relationship between the <i>PTGS1</i> 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. <i>Conclusions:</i> Our data suggest that the <i>PTGS1</i> P17L genotype contributes to response to aspirin as assessed by ex-vivo platelet aggregation. Our data further suggest that the association between <i>PTGS1</i> genotype and aspirin response might vary by ethnicity.