Platelet Glycoprotein IIIa Polymorphism Research Articles

Association of platelet glycoprotein IIIa polymorphism as a risk factor for acute ischemic stroke in Egyptian patients

Association of platelet glycoprotein IIIa polymorphism as a risk factor for acute ischemic stroke in Egyptian patients

Frequência do polimorfismo da glicoproteína IIIa de plaquetas (PlA2) em mulheres com diabetes mellitus tipo 2

O polimorfismo da glicoproteína IIIa de plaquetas está associado a um aumento no risco de doenças arteriais coronarianas. Mulheres com diabetes mellitus tipo 2 apresentam um aumento de cinco vezes no risco para doenças arteriais coronarianas quando comparadas com mulheres não-diabéticas. O objetivo do presente estudo foi verificar a frequência do polimorfismo da glicoproteína IIIa (PlA2) em mulheres com diabetes mellitus tipo 2 e comparar com a frequência descrita na literatura. A análise do polimorfismo PlA2 foi realizada para 62 mulheres com diabetes mellitus tipo 2 através da reação em cadeia da polimerase seguida de análise do polimorfismo de tamanho de fragmento de restrição (PCR-RFLP). As frequências observadas foram 81% para PlA1A1, 18% para PlA1A2 e 1% para PlA2A2. Não houve diferença significativa entre as frequências observadas e as frequências descritas na literatura. Nossos resultados sugerem que a frequência do polimorfismo PlA2 em mulheres com diabetes mellitus tipo 2 é a mesma observada na população em geral.

Investigation of platelet glycoprotein IIIa polymorphism using flow cytometry in patients with rheumatoid arthritis

Objectives: Previous work has shown that the human platelet antigen (HPA) 1b polymorphism of platelet glycoprotein IIIa (GPIIIa) is implicated in the development of ischaemic vascular disease. HPA1b positive platelets have a lower threshold for activation and may exert a greater thrombotic tendency than those without the 1b allele. However, platelets heterozygous for the polymorphism are also more sensitive to aspirin than those homozygous for the 1b allele, which have a similar sensitivity to those without the 1b allele. A flow cytometric method has become available to identify this polymorphism. The aim of our study was to evaluate the use of this assay in patients with rheumatoid arthritis (RA) and to determine the incidence of the 1b allele in these patients. We also compared platelet aggregation and platelet/white blood cell interaction in patients with or without this polymorphism.Methods: We enrolled 99 patients and measured platelet aggregation in whole blood and platelet‐rich plasma (prp), platelet/white blood cell interaction and C‐reactive protein (CRP).Results: Thirty‐four of the 99 patients were unsuitable for analysis because their baseline expression of GPIIIa was outwith the normal range, making the results outwith the limits of the flow cytometric method. The incidence of the 1b allele in the patients was 29%, with incidence being higher in females, although this failed to reach statistical significance. The number of circulating platelet aggregates and adenosine diphosphate (ADP)‐induced aggregation in prp was significantly higher in those patients with the 1b allele.Conclusions: This method may be of use as an initial screening test.

Prediction of the excessive perioperative bleeding in patients undergoing coronary artery bypass grafting: Role of aspirin and platelet glycoprotein IIIa polymorphism

The presence of the glycoprotein IIIa allele PlA2 is associated with enhanced thrombin formation and an impaired antithrombotic action of aspirin, which could favor coronary thrombosis. We wondered whether PlA1/A2 genetic polymorphism could affect the postoperative bleeding in patients undergoing coronary artery bypass grafting. We also aimed to assess the effects of aspirin pretreatment and to ascertain the value of platelet function studies as predictors of postoperative bleeding. In a randomized, double-blind study, patients undergoing coronary artery bypass grafting were pretreated with a 150-mg dose of aspirin orally 12 and 3 hours before surgery (n = 51, 41 elective) or with placebo (n = 51, 43 elective). The hemostasis was monitored by Simplate (bioMérieux, Inc, Durham, NC) bleeding time and capillary closure time (platelet function analyzer PFA 100; Sysmex UK Ltd, Milton Keynes, United Kingdom). Postoperative bleeding and blood products transfusions were recorded. The glycoprotein IIIa polymorphism was analyzed. Bleeding was significantly greater in PlA1 homozygotes from control group. Blood loss was significantly greater (by 25%) in aspirin group. The volume of blood products transfusions in aspirin patients was significantly larger (by 137%). When subjects were stratified accordingly to blood platelet glycoprotein IIb/IIIa genotype, in the aspirin group PlA2 carriers had greater blood loss than PlA1 homozygotes (1858 +/- 932 mL vs 1216 +/- 525 mL, P < .05). PlA1 homozygotes normally had a greater risk of perioperative bleeding. Capillary closure time had no advantage relative to Simplate bleeding time in predicting postoperative blood loss. Aspirin pretreatment revealed no beneficial effects and resulted in increased postoperative bleeding and requirement for blood product transfusions after coronary artery bypass grafting in patients with stable angina. It was most unfavorable for PlA2 carriers.

Aspirin Resistance: An Evaluation of Current Evidence and Measurement Methods

Aspirin resistance is a poorly characterized phenomenon, whereby certain patients do not benefit from the antithrombotic effect of aspirin. The frequency of aspirin resistance is unknown, but estimates range from 5-60%. The mechanism of aspirin resistance also is unknown; proposed mechanisms are poor patient compliance, poor aspirin absorption, increased isoprostane activity, platelet hypersensitivity to agonists, increased cyclooxygenase-2 activity, a cyclooxygenase-1 polymorphism, and the platelet alloantigen 2 polymorphism of platelet glycoprotein IIIa. Aspirin resistance appears to be dose related in some patients and therefore may be overcome with high doses. Evidence indicates that aspirin resistance is a dynamic state, with significant intrapatient variability in aspirin sensitivity with time. To date, a sensitive and specific assay of aspirin effect that reliably predicts treatment failure has not emerged. However, several commercially available products are being marketed for this purpose without convincing clinical data. Despite a wealth of literature on the topic, aspirin resistance remains an enigma. Further investigation is needed regarding strategies to identify and treat patients resistant to aspirin.

The role of platelet glycoprotein IIIa polymorphism in the high prevalence of in vitro aspirin resistance in patients with intracoronary stent restenosis

The aim of our study was to determine the relation between platelet glycoprotein IIIa (Pl A ) polymorphism and aspirin resistance in patients with intracoronary stent restenosis. Clinically, aspirin resistance is defined as having thrombotic and embolic cardiovascular events despite regular aspirin therapy. Platelet glycoprotein IIIa polymorphism is said to be a possible mechanism of aspirin resistance. We studied the prevalence of aspirin resistance in 204 previously intracoronary stent-implanted patients with stable coronary artery disease. In 102 of these patients, intracoronary stent restenosis was present. Platelet functions were analyzed in a platelet function analyzer (PFA-100, Dade Behring, Germany) with collagen and/or epinephrine (Col/Epi) and collagen and/or adenosine diphosphate cartridges. Closure time <186 seconds was defined as aspirin resistance with Col/Epi cartridges of PFA-100. The Pl A polymorphisms of 43 aspirin-resistant and 51 aspirin-sensitive subjects were determined with polymerase chain reaction and restriction fragments length polymorphism. A total of 31.3% (n = 32) of patients with intracoronary stent restenosis and 10.7% (n = 11) of patients with patent intracoronary stents were resistant to aspirin by PFA-100. The Pl A1,A1 allele of glycoprotein IIIa was present in 36 subjects (83.7.%) and the Pl A1,A2 allele was present in 7 subjects (16.2.%) in the aspirin-resistant patients group. The Pl A1,A1 allele of glycoprotein IIIa was present in 37 subjects (72.5%) and the Pl A1,A2 allele was present in 14 subjects (27.5%) in the aspirin-sensitive patients group ( P = .195). Our results suggest that platelets of patients with intracoronary stent restenosis with or without Pl A2 heterozygosity of glycoprotein IIIa are more likely to be resistant to low-dose aspirin therapy.

The PlA1/A2 polymorphism of platelet glycoprotein IIIa is not associated with the risk of type 2 diabetes. The Ludwigshafen Risk and Cardiovascular Health Study

The PlA1/A2 polymorphism of platelet glycoprotein IIIa (GPIIIa) has been implicated in the pathogenesis of type 2 diabetes. We studied this polymorphism in a homogenous, extensively phenotyped cohort using the candidate gene approach. The PlA1/A2 polymorphism was determined in 1051 patients with type 2 diabetes and in 2247 individuals without type 2 diabetes. In patients with type 2 diabetes, genotype frequencies were as follows: PlA1/A1 71.4%, PlA1/A2 26.0%, and PlA2/A2 2.7%. In individuals without type 2 diabetes, genotype frequencies were 71.6%, 25.7% and 2.8%, respectively. The PlA2 allele was not associated with fasting and postprandial glucose, glycated haemoglobin, insulin, proinsulin, C-peptide and calculated indices of insulin resistance or pancreatic beta cell function. The PlA2 allele was also not significantly associated with angiographic CHD (adjusted odds ratio [OR] 1.13; 95% CI, 0.93-1.39) or with a history of previous myocardial infarction (adjusted OR 1.09; 95% CI, 0.87-1.37). The GPIIIa PlA1/A2 polymorphism is not associated with type 2 diabetes, glucose metabolism, angiographic CHD or myocardial infarction.

Effect of glycoprotein IIIa Pl A2 polymorphism on outcome of patients with stable coronary artery disease and effect of smoking

A polymorphism of glycoprotein IIb/IIIa has been associated with myocardial infarction and restenosis after percutaneous coronary intervention. The influence on outcome and the interaction of the Pl A1 genotype with classic risk factors for coronary artery disease (CAD) were characterized in patients with chronic CAD followed prospectively for 3 years. Pl A1 genotypes were assessed in 592 patients enrolled in the Medical, Angioplasty, or Surgery Study II, a randomized trial comparing treatments for patients with CAD and preserved left ventricular function. The incidence of the composite end point of cardiac death, myocardial infarction, and refractory angina requiring revascularization were determined in each genotype group. Risk was assessed with the Cox proportional-hazards model. The clinical characteristics and treatment of each genotype were similar. Although the composite end point tended to be more common in patients with the Pl A2 allele, only smokers with the Pl A2 allele had a significantly increased incidence of the composite end point (p = 0.01). Moreover, a 2.2-fold increased risk was apparent in smokers with the Pl A2 allele (p = 0.03). Thus, taken together, these data provide support for the interaction effect between smoking and the Pl A1 gene variant. Smokers with the Pl A2 polymorphism of platelet glycoprotein IIIa are at greater risk for subsequent cardiac events in stable coronary disease.

No evidence that the PLA1/PLA2 polymorphism of platelet glycoprotein IIIa is implicated in angiographically characterized coronary atherosclerosis and premature myocardial infarction

Platelet membrane glycoprotein IIb/IIIa plays an important role in platelet aggregation. A polymorphism of the gene encoding the IIIa subunit, with the two allele forms PLA1 and PLA2, has been identified. Some, but not all, studies suggest that the PLA2 allele confers an increased risk of suffering a myocardial infarction. Conversely, a recent study suggests that the PLA1 allele may contribute to early atherosclerosis and more rapid progression of stable coronary artery disease. To test whether these associations could be reproduced in a well-characterized sample of survivors of premature myocardial infarction, we examined 369 patients admitted to coronary care units in the Stockholm area who suffered a first myocardial infarction before the age of 60 years. There were no significant differences in extent of coronary artery disease according to PLA genotype group (based on quantitative coronary angiography). In addition, the frequencies of PLA1 and PLA2 alleles did not differ from those of 388 well-matched control subjects without coronary artery disease. These results suggest that the PLA1/PLA2 polymorphism of the platelet glycoprotein IIIa gene does not substantially contribute to the development of coronary atherosclerosis or the genetic susceptibility to premature myocardial infarction.

Plasminogen activator inhibitor type 1 (PAI1) and platelet glycoprotein IIIa (PGIIIa) polymorphisms in Black South Africans with pre-eclampsia.

Association of fibrin abnormalities with pre-eclampsia prompted this study to examine whether polymorphisms in the plasminogen activator inhibitor Type 1 and platelet glycoprotein IIIa genes constitute risk factors for this condition. A group of 151 Black Zulu-speaking pre-eclamptics was examined for 4G/5G plasminogen activator inhibitor Type 1 and PlA1/A2 platelet glycoprotein IIIa polymorphic alleles using standard techniques. Results were compared with those found in 217 ethnically matched healthy normotensive pregnant women who had normal full-term gestations. Pre-eclamptic patients had a slightly higher frequency of the 4G plasminogen activator inhibitor Type 1 allele (15%) compared with the controls (12%); this was reflected also in the heterozygote frequency (28% and 22%) for the patients and the controls, respectively. These differences were not significant. Only 2% of this population was found to be homozygous for the 4G allele. No differences were observed in the platelet glycoprotein IIIa polymorphism genotype and allele frequency distribution between the patients and the controls. Neither the 4G allele of the plasminogen activator inhibitor Type 1 nor the PlA2 allele of the platelet glycoprotein IIIa have any significant role as risk factors in the patho-etiology of pre-eclampsia in Black South Africans, although these genes cannot yet be excluded as contributory to this disorder. It is possible that the underlying causes of pre-eclampsia may vary between different ethnic populations.

Platelet PlA2 polymorphism and platelet activation are associated with increased troponin I release after cardiopulmonary bypass.

The PlA2 polymorphism of platelet glycoprotein IIIa has been identified as a prothrombotic risk factor in a number of cardiovascular settings. The aim of this study was to determine whether the PlA2 polymorphism of platelet glycoprotein IIIa and degree of platelet activation were associated with more severe myocardial injury as indicated by troponin I release following cardiopulmonary bypass. The PlA2 genotype was determined in 66 patients undergoing elective coronary artery bypass grafting requiring cardiopulmonary bypass. Troponin I concentrations and the percentage of circulating, activated (CD62P+) platelets were measured at predetermined intervals perioperatively. Forty-six patients were Pl(A1,A1), and 20 were Pl(A1,A2) or Pl(A2,A2). Patients with at least one PlA2 allele had significantly greater postoperative troponin I concentrations than PlA1 homozygotes (P = 0.006, analysis of variance). Peak troponin I concentrations also correlated significantly with the increase in circulating, activated platelets (P = 0.02, Spearman rank correlation). The PlA2 allele of platelet glycoprotein IIIa is associated with higher troponin I concentrations following cardiopulmonary bypass surgery, suggesting that this platelet polymorphism contributes to perioperative myocardial injury.

Platelet glycoprotein IIIa polymorphism is not a risk factor for target vessel revascularization after percutaneous revascularization Kimberly A. Skelding, Demetri Demetriou, Domnita Crisan, Laxmi Mehta, Judith A. Boura, Mark C. Pica, Debra A. Guido-Allen, Bohuslav Finta, Robert D. Safian, James A. Goldstein, Cindy L. Grines, William W. O'Neill. William Beaumont Hospital, Royal Oak, MI

Platelet glycoprotein IIIa polymorphism is not a risk factor for target vessel revascularization after percutaneous revascularization Kimberly A. Skelding, Demetri Demetriou, Domnita Crisan, Laxmi Mehta, Judith A. Boura, Mark C. Pica, Debra A. Guido-Allen, Bohuslav Finta, Robert D. Safian, James A. Goldstein, Cindy L. Grines, William W. O'Neill. William Beaumont Hospital, Royal Oak, MI

The PlA1/A2 Polymorphism of Platelet Glycoprotein IIIa Is not Associated with Peripheral Arterial Disease

The PlA1/A2 Polymorphism of Platelet Glycoprotein IIIa Is not Associated with Peripheral Arterial Disease -

The PLA1/A2 polymorphism of platelet glycoprotein IIIA is not associated with deep venous thrombosis

The PLA1/A2 polymorphism of platelet glycoprotein IIIA is not associated with deep venous thrombosis

The Prothrombin Gene G20210A Mutation and the Platelet Glycoprotein IIIa Polymorphism Pl A2 in Patients with Central Retinal Vein Occlusion

The prothrombin gene G20210A mutation and the platelet glycoprotein IIIa polymorphism Pl A2 have been shown to be associated with thromboembolic disease. We wondered if mutations were overrepresented in patients with central retinal vein occlusion. We studied 129 consecutive patients with a history of central retinal vein occlusion. We analysed for the prothrombin gene G20210A mutation and the platelet glycoprotein IIIa polymorphism Pl A2 and compared the results to controls with no history of thrombosis. For the platelet glycoprotein IIIa polymorphism Pl A2, 69% were normal, 26% were heterozygous, and 5% were homozygous. For the G20210A prothrombin mutation, 97% were normal and 3% were heterozygous. Neither the prothrombin gene G20210A mutation nor the platelet glycoprotein IIIa polymorphism Pl A2 seem to be associated with central retinal vein occlusion.

PlA polymorphism of platelet glycoprotein IIIa and risk of restenosis after coronary stent placement.

Platelets play a central role in the process of restenosis after percutaneous coronary interventions. A polymorphism of platelet glycoprotein IIIa (PlA) has been associated with a higher risk of coronary thrombosis. We designed this prospective study to test the hypothesis that PlA polymorphism of glycoprotein IIIa is associated with an increased risk for restenosis after coronary stent placement. The study included 1150 consecutive patients with successful coronary stent placement and 6-month follow-up with coronary angiography. The end point of the study was the incidence of angiographic restenosis (>/=50% diameter stenosis) at follow-up. Of the 1150 patients, 72.5% were homozygous for PlA1, 24.7% were heterozygous (PlA1/A2), and 2.8% were homozygous for PlA2. Patients with the PlA2 allele demonstrated a significantly higher restenosis rate than did those without (47% versus 38%; OR, 1.42; 95% CI, 1.09 to 1.84). The risk was highest in homozygous carriers of PlA2 (53.1% restenosis rate). After adjustment for several clinical and angiographic characteristics, the presence of the PlA2 allele remained a significantly independent risk factor for restenosis (adjusted OR, 1.35; 95% CI, 1.07 to 1.70). The influence of the PlA2 allele on restenosis was stronger in women. Women with PlA2 had a restenosis rate of 52% compared with the 33% incidence among women homozygous for PlA1 (OR, 2.21; 95% CI, 1.27 to 3.85). This study showed a significant association between the PlA polymorphism of glycoprotein IIIa and the risk of restenosis after coronary stent placement. The risk was more pronounced in patients homozygous for PlA2 allele and in female patients.

Pl A1/A2 polymorphism of platelet glycoprotein IIIa and risk of acute coronary syndromes in heterozygous familial hypercholesterolemia

Familial hypercholesterolemia (FH) is an autosomal inherited disorder caused by different mutations in the low density lipoprotein (LDL) receptor gene. It has been demonstrated that there is an increased risk of coronary heart disease (CHD) in heterozygous FH subjects, although this excess CHD is not only explained by the LDL-cholesterol concentration or the class of the LDL-receptor mutation. To investigate if a common polymorphism at the platelet glycoprotein (GP) IIIa gene locus could be related to CHD phenotypic variation in heterozygous FH, we have carried out a case-control study. We have studied 40 cases and 40 controls matched for age, sex and genetic defect in the LDL-receptor gene. Allele frequency of Pl A2 polymorphism for cases and controls was 20 and 22.5%, respectively, and the difference was not significant. In conclusion, our data do not support any association between the GP IIIa polymorphism and the increased prevalence of acute coronary syndromes in the heterozygous FH subjects.

Platelet glycoprotein IIIa polymorphism, aspirin, and thrombin generation

Platelet glycoprotein IIIa polymorphism, aspirin, and thrombin generation

Genetic polymorphism of platelet glycoprotein IIIa in patients with acute myocardial infarction and acute ischaemic stroke.

It has recently been suggested that the Leu33Pro polymorphism of the platelet glycoprotein IIIa affects the risk of coronary thrombosis. Finland is genetically isolated and has an incidence of cardiovascular disease among the highest in the world. Interestingly, the prevalence of ischaemic heart disease also varies in different parts of the country, being highest in eastern Finland. We studied the Leu33Pro polymorphism using polymerase chain reaction in 133 patients with coronary artery disease, 234 patients with cerebrovascular disease and 326 control subjects originating from two areas of Finland. The frequencies of the Pro33 allele in the patients with acute myocardial infarction and cerebrovascular attack were 13% and 14%, respectively, and did not differ from the controls (13%). Among patients with acute myocardial infarction from the Helsinki area, the family history of premature coronary artery disease was more often positive in carriers of the Pro33 allele than in non-carriers, but after adjustment for multiple comparisons the difference was no longer significant. We could not confirm the original observation that the Pro33 allele constitutes an independent risk factor for coronary artery disease. Further studies are needed to clarify whether co-occurrence of Pro33 and some unrecognized inherited factor pose an additional risk of vascular disease.

The relationship betwen smoking and triglyceride-rich lipoproteins is modulated by genetic variation in the glycoprotein IIIa gene

In the last year, several studies have reported conflicting results concerning an association between the PI A2 allele of the PI A1 A2 polymorphism of platelet glycoprotein IIIa and the risk of myocardial infarction. In the present study, we analyzed the hypothesis of whether glycoprotein IIIa genotypes have any association with lipids and lipoproteins as classical cardiovascular risk factors. Smoking, associated with changes in triglyceride-rich lipoprotein (TRL) concentrations and with both hypercoagulability and reduced fibrinolysis, was also analyzed as an environmental factor. Blood samples were obtained from 170 subjects (83 men and 87 women; mean age, 57 years; SD 15) recruited by random sampling from the census of Girona, Spain. Subjects were classified as current smokers (n = 41) and nonsmokers or exsmokers (n = 129). Whereas no differences were found in lipid and lipoprotein concentrations between smokers and nonsmokers in subjects with the PI A1 A1 genotype, smokers with the PI A1 A2 or PI A2 A2 genotypes showed significantly higher triglyceride and very—low-density lipoprotein (VLDL) triglyceride concentrations than nonsmokers or exsmokers with the same genotypes. Similarly, the VLDL triglyceride/HDL cholesterol ratio was significantly different in subjects with the PI A1 A2 or PI A2 A2 genotypes stratified according to smoking status. Further analysis revealed a significant interaction between smoking and genotype when those homozygous for the allele PI A1 were compared with one or two PI A2 alleles for the three lipid parameters. The observed effects appear to show links between smoking, triglyceride metabolism, and a glycoprotein involved in platelet aggregation. It is likely that the PI A polymorphism is in linkage disequilibrium with other functional mutations that might influence triglyceride metabolism under some environmental factors such as smoking. This finding may provide a new perspective in the complex relationship between glycoprotein IIIa gene, environment, and their interactions.