Cyclooxygenase-1 haplotype modulates platelet response to aspirin

Maree, Andrew O.; Curtin, Ronan J.; Chubb, Anthony J.; Dolan, Ciara; Cox, Dermot; O’Brien, John; Crean, Peter; Shields, Denis C.; Fitzgerald, Desmond J.

doi:10.1111/j.1538-7836.2005.01555.x

Cited by 200 publications

(133 citation statements)

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“…Similarly, Colaizzo et al 19) revealed an association between the COX-2 G765C polymorphism and cerebrovascular ischemia, suggesting that the COX-2 gene is a susceptibility locus for the risk of cerebrovascular ischemic disease; however, Cipollone et al 20) found that the COX-2 G765C polymorphism could reduce urine 11-dehydro-thromboxane B2 (11-dTxB2) and was a protective factor against myocardial infarction and ischemic stroke. In addition, Frelinger et al 21) and Meen et al 22) have shown that AR in a number of subjects may be independent of both COX-1 and COX-2; however, Maree et al 23) showed that genetic variability in COX-1 appears to modulate both arachidonic acid (AA)-induced platelet aggregation and thromboxane generation. Heterogeneity in the way patients respond to aspirin may in part reflect COX-1 genotype variations.…”

Section: Study Populationsmentioning

confidence: 99%

Platelet Response to Aspirin in Chinese Stroke Patients is Independent of Genetic Polymorphisms of COX-1 C50T and COX-2 G765C

Zhou

Lin

et al. 2013

JAT

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Aim: Aspirin resistance (AR) is common in Chinese stroke patients taking antiplatelet medications; however, few studies have documented the role of cyclooxygenase (COX)-1 C50T and COX-2 G765C polymorphisms in AR. The aim of this study was to investigate the prevalence of AR in Chinese stroke patients and the relationships between AR and COX-1 C50T and COX-2 G765C polymorphisms, and to evaluate the effect of these polymorphisms on platelet response to aspirin. Methods: We prospectively enrolled 634 Chinese stroke patients. Platelet aggregation testing was performed before and after aspirin administration. The pre-and post-aspirin levels of 11-dehydrothromboxane B2 (11-dTxB2) were determined in urine samples. COX-1 C50T and COX-2 G765C genotypes were determined by a polymerase chain reaction-allelic restriction assay. Results: AR was detected in 129 patients (20.4%), aspirin semi-resistance (ASR) was detected in 28 patients (4.4%), and aspirin sensitivity (AS) was detected in 477 patients (75.2%). There was no association between COX-1 C50T or COX-2 G765C polymorphisms and ASR＋AR. Aspirin could efficiently reduce 11-dTxB2 production by approximately 75%. In addition, platelet aggregation, both in response to arachidonic acid (AA) and adenosine 5'-diphosphate (ADP), was inhibited by more than 80% and 40%, respectively; however, the percentage reduction in platelet aggregation and 11-dTxB2 levels was not significantly different between the COX-1 C50T and COX-2 G765C genotypes (p＞0.05). Conclusions: There was no association between COX-1 C50T and COX-2 G765C polymorphisms and AR in Chinese stroke patients. In addition, COX-1 C50T and COX-2 G765C polymorphisms had no effect on the platelet response to aspirin. J Atheroscler Thromb, 2013; 20:65-72.

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Section: Study Populationsmentioning

confidence: 99%

Platelet Response to Aspirin in Chinese Stroke Patients is Independent of Genetic Polymorphisms of COX-1 C50T and COX-2 G765C

Zhou

Lin

et al. 2013

JAT

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“…ADP receptor P2Y12 (P2RY12 G52T) 4 ; 12. Prostaglandin G/H synthase 1 (cyclooxygenase-1) (PTGS1 C50T) 43 ; and 13. TXA2 receptor (TBXA2R C795T or C924T or G1686A).…”

Section: Candidate Gene Association Studiesmentioning

confidence: 99%

The genetics of normal platelet reactivity

Kunicki

Nugent

2010

Blood

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Genetic and environmental factors contribute to a substantial variation in platelet function seen among normal persons. Candidate gene association studies represent a valiant effort to define the genetic component in an era where genetic tools were limited, but the single nucleotide polymorphisms identified in those studies need to be validated by more objective, comprehensive approaches, such as genome-wide association studies (GWASs) of quantitative functional traits in much larger cohorts of more carefully selected normal subjects. During the past year, platelet count and mean platelet volume, which indirectly affect platelet function, were the subjects of GWAS. IntroductionInterindividual platelet responsiveness to a variety of agonists is highly variable, as documented in several studies of large cohorts of normal persons. [1][2][3][4][5][6][7][8][9][10][11][12] At the same time, these and other studies of siblings, twins, and families with a history of coronary artery disease (CAD) have documented that intraindividual responsiveness is highly reproducible over time, regardless of the agonist tested or the chosen method of assessment. These findings strongly suggest that there is a high level of heritability of platelet function, and this has prompted numerous attempts to define the genetic basis for platelet function variability. A summary of platelet functionTo fully appreciate the gene association studies, it is necessary to briefly summarize key aspects of platelet function and establish a molecular and physiologic basis for the selection of genes to study.When a blood vessel is damaged, circulating platelets interact with components of the extracellular matrix, particularly collagen, and a complex series of receptor-ligand interactions ensues that ultimately leads to the formation of a stable platelet plug or thrombus. This process is a continuum of at least 3 phases that we can describe as initiation, extension, and consolidation, each of which entails the cooperation of a different group of receptors.In the initiation phase, plasma von Willebrand factor (VWF) binds to collagen via its A3 domain and becomes structurally altered such that its A1 domain then binds to the platelet membrane receptor glycoprotein Ib-IX-V complex (GPIb complex). It is the GPIb␣ or larger subunit of GPIb that makes direct contact with VWF. This association is a requisite step in the adhesion of platelets to exposed thrombogenic surfaces at sites of vessel wall injury or in regions of atherosclerotic plaque rupture. Concurrently, a more stable platelet monolayer is formed on the collagen surface mediated predominantly by the platelet-specific receptor glycoprotein VI (GPVI) and platelet integrin ␣ 2 ␤ 1 .The engagement of these receptors enhances platelet activation leading to the extension phase, mediated largely by the conversion of prothrombin to thrombin at the activated platelet surface and the secretion of active compounds from platelet granules (␣-granules and ␦-granules), which can further stimulate platelets. One of...

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“…sequence variation in CoX-1 as it relates to aspirin response has been investigated, with studies yielding inconsistent data. 15,16 similar studies have been concluded with respect to snps that reside within the glycoprotein iiia gene. these too have led to contradictory findings.…”

Section: Pharmacogenomics Of Aspirinmentioning

confidence: 72%

Cardiovascular Drugs and the Genetic Response

Dandona

2014

Methodist DeBakey Cardiovascular Journal

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Cyclooxygenase-1 haplotype modulates platelet response to aspirin

Cited by 200 publications

References 15 publications

Platelet Response to Aspirin in Chinese Stroke Patients is Independent of Genetic Polymorphisms of COX-1 C50T and COX-2 G765C

Platelet Response to Aspirin in Chinese Stroke Patients is Independent of Genetic Polymorphisms of COX-1 C50T and COX-2 G765C

The genetics of normal platelet reactivity

Cardiovascular Drugs and the Genetic Response

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