Lack of association between the P2Y12 receptor gene polymorphism and platelet response to clopidogrel in patients with coronary artery disease

Angiolillo, Dominick J.; Fernández‐Ortíz, Antonio; Bernardo, Esther; Ramı́rez, Carlos A.; Cavallari, Ugo; Trabetti, Elisabetta; Sabaté, Manel; Jiménez‐Quevedo, Pilar; Hernández, Rosana; Moreno, Raúl; Escaned, Javier; Alfonso, Fernándo; Bañuelos, Camino; Costa, Marco A.; Bass, Theodore A.; Pignatti, Pier Franco; Macaya, Carlos

doi:10.1016/j.thromres.2005.03.001

Cited by 137 publications

(78 citation statements)

References 23 publications

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“…Similarly, a cross-sectional study in 112 Iranian patients reported that 25.9% of them were nonresponders to clopidogrel (Namazi et al 2012). However, in a smaller study of 36 patients with 300 mg loading dose and 83 patients with 75 mg/d of maintenance dose of clopidogrel, the P2Y12 receptor haplotypes were not associated with clopidogrel response variability (Angiolillo et al 2005). Hence, further genotype-phenotype association studies are required to show the possibility of this particular polymorphism in the development of CAD, PVD, and clopidogrel response variability, which is considered as one of the limitations of our study.…”

Section: Discussionmentioning

confidence: 95%

Frequency of single nucleotide platelet receptor gene polymorphism (P2Y12-i744T>C) in coronary artery disease patients among Tamilian population

et al. 2017

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Several factors contribute to the development of coronary artery disease (CAD). Adenosine diphosphate (ADP) activated P2Y12 receptor also plays a key role in platelet activation and aggregation. It has been found that common variation in the P2Y12 gene was associated with increased platelet aggregation resulting in adverse cardiovascular outcomes. Thus, polymorphisms in the ADP receptor P2Y12 may contribute to the development of CAD. This study aims to determine the frequency distribution of platelet receptor polymorphism P2Y12 (i744T>C) in Tamilian population and to predict its possible role in CAD. Three hundred seventyone subjects were recruited comprising of 221 healthy volunteers and 150 patients with CAD belonging to either sex, aged 18-60 years of Tamilian origin. Genomic DNA was extracted using phenol-chloroform method. Genotyping was done by PCR-RFLP (Polymerase chain reaction-restriction fragment length polymorphism). The C allele frequency of P2Y12 polymorphism in controls and cases was 8.4% and 17.7%, respectively. The TT, TC, and CC genotype frequencies in controls and cases were 83.7%, 15.8%, 0.5% and 66.7%, 31.3%, 2%, respectively. The genotype frequencies were in HardyWeinberg equilibrium. There was a significant association (p < 0.05) between the mutant genotypes of P2Y12 (i744T>C) polymorphism and risk of CAD. The odds ratio was found to be 2.6. The variant allele frequency of P2Y12-i744T>C was significantly different from other populations. There was a significant association between the mutant genotypes of P2Y12 (i744T>C) polymorphism and risk of developing CAD. Thus, the present study will emphasize on the relevance of pharmacogenetic testing of P2Y12 (i744T>C) receptor gene polymorphism in CAD patients.

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Section: Discussionmentioning

confidence: 95%

Frequency of single nucleotide platelet receptor gene polymorphism (P2Y12-i744T>C) in coronary artery disease patients among Tamilian population

et al. 2017

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“…9 Genetic defects of the ADP receptor do not seem to play a major role in this phenomenon. 10,11 Therefore, it is probable that individual differences in clopidogrel absorption and metabolization cause the wide range in response.…”

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confidence: 99%

Monitoring of Clopidogrel-Related Platelet Inhibition: Correlation of Nonresponse with Clinical Outcome in Supra-Aortic Stenting

Müller-Schunk¹,

Linn²,

Peters³

et al. 2008

AJNR Am J Neuroradiol

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BACKGROUND AND PURPOSE:Clopidogrel and aspirin are antiplatelet medications used in patients intended for endovascular stent placement. Although various studies have investigated individual responsiveness to clopidogrel in patients undergoing coronary interventions, there are no studies regarding patients undergoing stent placement of supra-aortic arteries supplying the brain. We analyzed platelet function in a near-patient setting to determine the effects of antiplatelet treatment in neurologic patients and correlated the results with clinical outcome after stent placement.

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“…Several studies tested the hypothesis that common polymorphisms of the P2Y 12 gene might interfere with the antiplatelet effects of drugs inhibiting the P2Y 12 receptor, accounting for the well known individual variability in the response to these agents [52,53]. The vast majority of these studies, with few exceptions, reported that P2Y 12 polymorphisms are not associated with altered platelet function inhibition by P2Y 12 antagonists [54][55][56][57][58][59][60][61]. …”

Section: Treatmentmentioning

confidence: 99%

Molecular defects of the platelet P2 receptors

Cattaneo

2011

Purinergic Signalling

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Human platelets express three types of P2 receptors, which play important roles in platelet function: P2X 1 , P2Y 1 and P2Y 12 . Only patients with either quantitative or qualitative abnormalities of the platelet P2Y 12 receptor have been well-characterized so far. Deficiencies of P2Y 12 are associated with nucleotide deletions in the open-reading frame, frameshifts, and early truncation of the protein, or with a nucleotide substitution in the transduction initiation codon. Congenital dysfunctions of P2Y 12 are associated with molecular defects involving the sixth trans-membrane domain or the adjacent third extracellular loop of the receptor, which identify a region of the protein whose integrity is necessary for normal receptor function. A mutation, predicting a lysine to glutamate (Lys174Glu) substitution was associated with decreased ligand binding to the receptor, suggesting that it is responsible for disruption of the adenosine diphosphate (ADP)-binding site of the receptor. Patients with P2Y 12 defects display a mild-tomoderate bleeding diathesis, characterized by mucocutaneous bleedings and excessive post-surgical and posttraumatic blood loss. Defects of P2Y 12 should be suspected when ADP, even at high concentrations (≥10 μM), is unable to induce full, irreversible platelet aggregation. Tests that evaluate the degree of inhibition of adenylyl cyclase by ADP should be used to confirm the diagnosis.

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Lack of association between the P2Y12 receptor gene polymorphism and platelet response to clopidogrel in patients with coronary artery disease

Cited by 137 publications

References 23 publications

Frequency of single nucleotide platelet receptor gene polymorphism (P2Y12-i744T>C) in coronary artery disease patients among Tamilian population

Frequency of single nucleotide platelet receptor gene polymorphism (P2Y12-i744T>C) in coronary artery disease patients among Tamilian population

Monitoring of Clopidogrel-Related Platelet Inhibition: Correlation of Nonresponse with Clinical Outcome in Supra-Aortic Stenting

Molecular defects of the platelet P2 receptors

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