Pharmacogenetics of aspirin resistance: a comprehensive systematic review

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Abstract
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• A genetic basis for aspirin resistance has been postulated to exist.• The individual studies published have been too small to allow reliable conclusions to be drawn.• In order to clarify what, if any, genetic basis exists for aspirin resistance, we have undertaken, to our knowledge, the largest and most comprehensive systematic review conducted to‐date in this field.WHAT THIS STUDY ADDS• There is a significant association between the PlA1/A2 molecular variant and aspirin resistance in healthy subjects, with the effect diminishing in the presence of cardiovascular disease.• However further studies are needed to confirm this.• We argue that investigators now need to agree on a standard technique to measure and define aspirin resistance.AIMSThe aim was to perform a systematic review of all candidate gene association studies in aspirin resistance.METHODSElectronic 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.RESULTSWithin 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.CONCLUSIONSOur 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.