Pharmacogenetics of aspirin resistance: a comprehensive systematic review.
OBJECTIVE
The aim was to perform a systematic review of all candidate gene association studies in aspirin resistance.


METHODS
Electronic databases were searched up until 1 December 2007 for all studies investigating any candidate gene for aspirin resistance in humans. Aspirin resistance was required to have been measured by a standardized laboratory technique to be included in the analysis.


RESULTS
Within 31 studies, 50 polymorphisms in 11 genes were investigated in 2834 subjects. The PlA1/A2 polymorphism in the GPIIIa platelet receptor was the most frequently investigated, with 19 studies in 1389 subjects. The PlA1/A2 variant was significantly associated with aspirin resistance when measured in healthy subjects [odds ratio (OR) 2.36, 95% confidence interval (CI) 1.24, 4.49; P = 0.009]. Combining genetic data from all studies (comprising both healthy subjects and those with cardiovascular disease) reduced the observed effect size (OR 1.14, 95% CI 0.84, 1.54; P = 0.40). Moreover, the observed effect of PlA1/A2 genotype varied depending on the methodology used for determining aspirin sensitivity/resistance. No significant association was found with aspirin resistance in four other investigated polymorphisms in the COX-1, GPla, P2Y1 or P2Y12 genes.


CONCLUSIONS
Our data support a genetic association between the PlA1/A2 molecular variant and aspirin resistance in healthy subjects, with the effect diminishing in the presence of cardiovascular disease. The laboratory methodology used influences the detection of aspirin resistance. However, as heterogeneity was significant and our results are based on a limited number of studies, further studies are required to confirm our findings.
Goodman
Timothy
T
Imperial College Cerebrovascular Research Unit (ICCRU), Hammersmith Hospitals, London, UK.
Ferro
Albert
A
Sharma
Pankaj
P
D001241:Aspirin / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000235:genetics; D051545:Cyclooxygenase 1 / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D005838:Genotype; D006801:Humans; D010597:Pharmacogenetics; D010974:Platelet Aggregation / Q000235:genetics; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011110:Polymorphism, Genetic / Q000187:drug effects* / Q000235:genetics
D010975:Platelet Aggregation Inhibitors; D051545:Cyclooxygenase 1; D001241:Aspirin