Meta-analysis of the association of platelet glycoprotein IIIa PlA1/A2 polymorphism with myocardial infarction

Zhu, Michael M; Weedon, Jeremy; Clark, Luther T.

doi:10.1016/s0002-9149(00)01136-x

Cited by 69 publications

(51 citation statements)

References 36 publications

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“…Only 11 (2%) patients were homozygous for Pl A2 /Pl A2 (CC). The aforementioned gene frequencies were similar to those previously reported and were in agreement with those predicted by Hardy-Weinberg equilibrium (11,15). Seventy-five percent of white and 74% of black patients were homozygous for the Pl A1 /Pl A1 (TT) genotype.…”

Section: Renal Transplant Recipient Demographics and Genotype Frequensupporting

confidence: 90%

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Role of β3 Integrin in Acute Renal Allograft Rejection in Humans

Chandrakantan

McDermott

Tran

et al. 2007

Clinical Journal of the American Society of Nephrology

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Background and objectives: ␤3 Integrin may play a role in the process of acute rejection by increasing leukocyte adhesion to the endothelium, cytotoxic T lymphocyte activation, and platelet aggregation.Design, setting, participants, & measurements: For investigation of the role of ␤3 integrin in the pathogenesis of acute rejection, this study examined the surface expression of ␤3 integrin on leukocyte subsets and analyzed a common singlenucleotide polymorphism in exon 2 of the gene encoding the ␤3 subunit that generates two ␤3 integrin isoforms, termed Pl

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Section: Renal Transplant Recipient Demographics and Genotype Frequensupporting

confidence: 90%

“…This genetic variant has been found to affect functionally the platelet response to various agonists in vitro (11). The Pl A polymorphism has been associated with a higher incidence of acute coronary syndromes as well as with a higher rate of restenosis after angioplasty (12).…”

mentioning

confidence: 99%

Role of β3 Integrin in Acute Renal Allograft Rejection in Humans

Chandrakantan

McDermott

Tran

et al. 2007

Clinical Journal of the American Society of Nephrology

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“…8 Epidemiological studies, however, gave inconsistent results, questioning the role of the Pl A2 polymorphism as a genetic coronary risk factor. 9 All the observations suggesting that the Pl A2 allele is a risk factor for arterial thrombosis rather than for atherosclerosis led to the concept that the Pro33 substitution in ␤ 3 integrins may induce a hypercoagulable state, most likely through platelet hyperaggregability. Platelet reactivity, however, was reported to be increased, 10 decreased, 11 or unaltered 12 in the Pl A2 carriers.…”

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confidence: 99%

Pl ^A2 Polymorphism of β ₃ Integrins Is Associated With Enhanced Thrombin Generation and Impaired Antithrombotic Action of Aspirin at the Site of Microvascular Injury

et al. 2001

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Background-Mechanisms by which the Pl A2 (Leu33Pro) polymorphism of ␤ 3 integrins could lead to an increased risk for coronary events are unclear. This study was designed to examine the effect of this polymorphism on blood coagulation. Methods and Results-In normal subjects (12 with Pl A1A1 , 9 with Pl A1A2 , and 3 with Pl A2A2 ), we evaluated the activation of prothrombin, factor V, and factor XIII and fibrinogen removal by quantitative immunoblotting; thrombinantithrombin III complex generation using ELISA; and levels of fibrinopeptide A and B by high-performance liquid chromatography in blood collected every 30 seconds at sites of standardized microvascular injury before and after 7 days of aspirin ingestion (75 mg

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“…The Pl A2 allele, present in approximately 20% of whites, has been reported to increase the risk of coronary thrombosis, 49 although the available data are inconsistent. 50 The same is true for platelet reactivity in the presence of the Pl A2 allele. [51][52][53] While studying platelet response to aspirin, Cooke et al 54 reported impaired aggregability of platelets obtained from subjects carrying the Pl A2 allele.…”

Section: Aspirin and The Fibrin Network Influence Of Polymorphismsmentioning

confidence: 90%

Antithrombotic properties of aspirin and resistance to aspirin: beyond strictly antiplatelet actions

Undas

Brummel‐Ziedins

Mann

2006

Blood

202

135

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Aspirin is effective in the prevention of cardiovascular events in high-risk patients. The primary established effect of aspirin on hemostasis is to impair platelet aggregation via inhibition of platelet thromboxane A 2 synthesis, thus reducing thrombus formation on the surface of the damaged arterial wall. Growing evidence also indicates that aspirin exerts additional antithrombotic effects, which appear to some extent unrelated to platelet thromboxane A 2 production. Aspirin can reduce thrombin generation with the subsequent attenuation of thrombin-mediated coagulant reactions such as factor XIII activation. Aspirin also acetylates lysine residues in fibrinogen resulting in increased fibrin clot permeability and enhanced clot lysis as well as directly promoting fibrinolysis with high-dose aspirin. The variable effectiveness of aspirin in terms of clinical outcomes and laboratory findings, which has been termed aspirin resistance, may be related to these additional antithrombotic effects that are altered when associated with common genetic polymorphisms such as the Leu33Pro ␤ 3 -integrin or Val34Leu factor XIII mutations. However, the clinical relevance of these observations is still un- IntroductionAcetylsalicylic acid, or aspirin, was synthesized by Hoffmann in 1898. Initially, this simple chemical compound was used as an antipyretic and anti-inflammatory agent. In the late 1960s aspirin emerged as a potent agent that prolongs the bleeding time and inhibits platelet aggregation. 1 During the last 30 years, many studies have reinforced aspirin's position in the armamentarium of physicians as an antithrombotic wonder drug that has saved the lives of millions of patients with cardiovascular disease. 2 Compelling evidence indicates that therapy with aspirin results in a 25% reduced risk of nonfatal myocardial infarction, nonfatal stroke, or vascular death in high-risk patients, regardless of sex, age, the presence of arterial hypertension, or diabetes. 3 In this article we review a number of the reported effects of aspirin on 3 basic elements of hemostasis: platelet activation and aggregation, the formation of the fibrin network, and the fibrinolytic process (Figure 1). A role of these effects in the phenomenon of aspirin resistance will also be discussed. Platelet activation and aggregation COX-dependent actions of aspirinThe conversion of arachidonic acid to various eicosanoids is regulated by the enzyme cyclooxygenase (COX) of which there are 2 isoforms: COX-1 and COX-2. 4 The COX-1 isoform, present in all tissues, represents the constitutive form of the enzyme, whereas the COX-2 isoform is expressed in inflammatory states in response to oxygen reactive species, endotoxins, cytokines, or growth factors. 5 COX-2 can be found in human atherosclerotic plaques 6 and also in small amounts in newly formed platelets. 7The aspirin-sensitive pathway in platelets initiates the release of arachidonic acid from membrane phospholipids. Aspirin inhibits the COX activity of prostaglandin (PG) G/H synthase (PGHS), by acetyla...

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Meta-analysis of the association of platelet glycoprotein IIIa PlA1/A2 polymorphism with myocardial infarction

Cited by 69 publications

References 36 publications

Role of β3 Integrin in Acute Renal Allograft Rejection in Humans

Role of β3 Integrin in Acute Renal Allograft Rejection in Humans

Pl ^A2 Polymorphism of β ₃ Integrins Is Associated With Enhanced Thrombin Generation and Impaired Antithrombotic Action of Aspirin at the Site of Microvascular Injury

Antithrombotic properties of aspirin and resistance to aspirin: beyond strictly antiplatelet actions

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Meta-analysis of the association of platelet glycoprotein IIIa PlA1/A2 polymorphism with myocardial infarction

Cited by 69 publications

References 36 publications

Role of β3 Integrin in Acute Renal Allograft Rejection in Humans

Role of β3 Integrin in Acute Renal Allograft Rejection in Humans

Pl A2 Polymorphism of β 3 Integrins Is Associated With Enhanced Thrombin Generation and Impaired Antithrombotic Action of Aspirin at the Site of Microvascular Injury

Antithrombotic properties of aspirin and resistance to aspirin: beyond strictly antiplatelet actions

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Pl ^A2 Polymorphism of β ₃ Integrins Is Associated With Enhanced Thrombin Generation and Impaired Antithrombotic Action of Aspirin at the Site of Microvascular Injury