Influence of cyclooxygenase-1 genotype on ex vivo aspirin response in patients at risk for stroke.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Momary
Kathryn M
KM
Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, Ill., USA. momary_km@mercer.edu
Shapiro
Nancy L
NL
Brace
Larry D
LD
Shord
Stacy S
SS
Grossi
Enzo
E
Viana
Marlos A
MA
Helgason
Cathy M
CM
Nutescu
Edith A
EA
Cavallari
Larisa H
LH
D001741:Black or African American / Q000208:ethnology / Q000235:genetics; D000368:Aged; D000483:Alleles; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use*; D051545:Cyclooxygenase 1 / Q000235:genetics*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology* / Q000208:ethnology / Q000517:prevention & control*; D016896:Treatment Outcome; D044465:White People / Q000208:ethnology / Q000235:genetics
D016861:Cyclooxygenase Inhibitors; D010975:Platelet Aggregation Inhibitors; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D001241:Aspirin