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Albert Ferro - One of the best experts on this subject based on the ideXlab platform.

  • Increased platelet expression of Glycoprotein IIIa following aspirin treatment in aspirin-resistant but not aspirin-sensitive subjects.
    British journal of clinical pharmacology, 2014
    Co-Authors: Christopher N. Floyd, Timothy Goodman, Silke Becker, Nan Chen, Agnesa Mustafa, Emma Schofield, James Campbell, Malcolm Ward, Pankaj Sharma, Albert Ferro
    Abstract:

    Aims Aspirin is widely used as an anti-platelet agent for cardiovascular prophylaxis. Despite aspirin treatment, many patients experience recurrent thrombotic events, and aspirin resistance may contribute to this. We examined the prevalence of aspirin resistance in a healthy population, and investigated whether the platelet proteome differed in aspirin-resistant subjects. Methods Ninety-three healthy subjects received aspirin 300 mg daily for 28 days. Before and at the end of treatment, urine was taken to determine 11-dehydrothromboxane B2, and blood was taken to measure arachidonic acid (AA)-induced aggregation of platelet-rich plasma and to interrogate the platelet proteome by mass spectrometric analysis with further confirmation of findings using Western blotting. Results In two of the 93 subjects, neither AA-induced aggregation nor urinary 11-dehydrothromboxane B2 was effectively suppressed by aspirin, despite measurable plasma salicylate concentrations, suggesting the presence of true aspirin resistance. Despite no detectable differences in the platelet proteome at baseline, following aspirin a marked increase was seen in platelet Glycoprotein IIIa expression in the aspirin-resistant but not aspirin-sensitive subjects. An increase in platelet Glycoprotein IIIa expression with aspirin resistance was confirmed in a separate cohort of 17 patients with stable coronary artery disease on long term aspirin treatment, four of whom exhibited aspirin resistance. Conclusions In a healthy population, true aspirin resistance is uncommon but exists. Resistance is associated with an increase in platelet Glycoprotein IIIa expression in response to aspirin. These data shed new light on the mechanism of aspirin resistance, and provide the potential to identify aspirin-resistant subjects using a novel biomarker.

  • The PlA1/A2 polymorphism of Glycoprotein IIIa as a risk factor for myocardial infarction: a meta-analysis.
    PloS one, 2014
    Co-Authors: Christopher N. Floyd, Agnesa Mustafa, Albert Ferro
    Abstract:

    Background The PlA2 polymorphism of Glycoprotein IIIa (GPIIIa) has been previously identified as being associated with myocardial infarction (MI), but whether this represents a true association is entirely unclear due to differences in findings from different studies. We performed a meta-analysis to evaluate whether this polymorphism is a risk factor for MI. Methods Electronic databases (MEDLINE and EMBASE) were searched for all articles evaluating genetic polymorphisms of GPIIIa. For studies where acute coronary events were recorded in association with genetic analysis, pooled odds ratios (ORs) were calculated using fixed-effects and random-effects models. The primary outcome measure was MI, and a secondary analysis was also performed for acute coronary syndromes (ACS) more generally. Findings 57 studies were eligible for statistical analysis and included 17,911 cases and 24,584 controls. Carriage of the PlA2 allele was significantly associated with MI (n = 40,692; OR 1.077, 95% CI 1.024–1.132; p = 0.004) but with significant publication bias (p = 0.040). The degree of association with MI increased with decreasing age of subjects (≤45 years old: n = 9,547; OR 1.205, 95% CI 1.067–1.360; p = 0.003) and with adjustment of data for conventional cardiovascular risk factors (n = 12,001; OR 1.240, 95% CI 1.117–1.376; p

  • The PlA1/A2 polymorphism of Glycoprotein IIIa as a risk factor for stroke: a systematic review and meta-analysis.
    PloS one, 2014
    Co-Authors: Christopher N. Floyd, Ben H Ellis, Albert Ferro
    Abstract:

    Background The PlA1/A2 polymorphism of Glycoprotein IIIa (GPIIIa) has been reported to be associated with risk of stroke in some studies, although other studies suggest no such association. This meta-analysis and systematic review was conducted to investigate the hypothesis that carriage of the PlA2 allele is a risk factor for stroke. Methods Electronic databases (MEDLINE and EMBASE) were searched for all articles evaluating carriage of the PlA2 allele and the incidence of stroke. Pooled odds ratios (ORs) were calculated using fixed-effect and random-effect models. Findings A total of 35 articles were eligible for inclusion, of which 25 studies were suitable for statistical analysis. For carriage of the PlA2 allele, OR 1.12 (n = 11,873; 95% CI = 1.03–1.22; p = 0.011) was observed for the incidence of stroke in adults, with subgroup analyses identifying the association driven by stroke of an ischaemic (n = 10,494; OR = 1.15, 95% CI = 1.05–1.27; p = 0.003) but not haemorrhagic aetiology (n = 2,470; OR = 0.90, 95% CI = 0.71–1.14; p = 0.398). This association with ischaemic stroke was strongest in individuals homozygous for the PlA2 allele compared to those homozygous for wild-type PlA1 (n = 5,906; OR = 1.74, 95% CI = 1.34–2.26; p 0.05). Conclusions The totality of published data supports the hypothesis that carriage of the PlA2 polymorphism of GPIIIa is a risk factor for ischaemic strokes, and specifically those of cardioembolic and large vessel origin.

  • The PlA1/A2 polymorphism of Glycoprotein IIIa in relation to efficacy of antiplatelet drugs: a systematic review and meta-analysis: The PlA1/A2 polymorphism and antiplatelet drug resistance
    British journal of clinical pharmacology, 2014
    Co-Authors: Christopher N. Floyd, Albert Ferro
    Abstract:

    Aim The PlA1/A2 polymorphism of Glycoprotein IIIa (GPIIIa) has been associated with both antiplatelet drug resistance and increased cardiovascular events. The aim of this study was to conduct the first meta-analysis investigating the association between carriage of the PlA2 allele and resistance to currently licensed antiplatelet drugs. Methods Electronic databases (MEDLINE and EMBASE) were searched for all articles evaluating genetic polymorphisms of GPIIIa. For studies where antiplatelet resistance was measured using validated techniques, pooled odds ratios (ORs) were calculated using fixed effects and random effects models. Results Sixteen studies were eligible for statistical analysis and included 1650 PlA1 homozygous subjects and 668 carriers of the PlA2 allele. For carriers of the PlA2 allele, OR 0.924 (n = 2318; 95% CI 0.743, 1.151; P = 0.481) was observed for resistance to any antiplatelet drug, OR 0.862 (n = 2085; 95% CI 0.685, 1.086; P = 0.208) for resistance to aspirin and OR 1.429 (n = 233; 95% CI 0.791, 2.582; P = 0.237) for resistance to clopidogrel. In the aspirin cohort, sub-group analysis revealed no statistical association in either healthy subjects or those with cardiovascular disease. PlA2 carriage was marginally associated with aspirin sensitivity using the fixed effects model when identified by the PFA-100 assay (n = 1151; OR 0.743, 95% CI 0.558, 0.989; P = 0.041) but with significant heterogeneity (I2 = 55%; P = 0.002). Significance was lost with analysis using a random effects model. Conclusions The totality of published data does not support an association between carriage of the PlA2 allele and antiplatelet drug resistance. Significant heterogeneity indicates the need for larger studies using validated and standardized assays.

  • Abstract W MP49: Carriage of the PlA2 Allele of Glycoprotein IIIa is Associated With an Increased Risk of Ischaemic Stroke: A Meta-Analysis
    Stroke, 2014
    Co-Authors: Ben H Ellis, Christopher N. Floyd, Albert Ferro
    Abstract:

    Introduction: The PlA1/A2 polymorphism of Glycoprotein IIIa has been associated with an increased risk of stroke, but with poor agreement between studies. Here we present a meta-analysis to assess the hypothesis that carriage of the PlA2 allele increases stroke risk. Methods: Electronic databases (MEDLINE and EMBASE) were searched for all articles evaluating carriage of the PlA2 allele and the incidence of stroke. Pooled odds ratios (ORs) were calculated using fixed-effect and random-effect models. Results: A total of 34 articles were eligible for statistical analysis (5,475 cases and 7,247 controls). For carriage of the PlA2 allele, OR 1.15 (n=12,115; 95% CI=1.05-1.26; p=0.002) was observed for total adult stroke, with sub-group analyses identifying an association with ischaemic (n=9,460; OR 1.22, 95% CI=1.10-1.35; p=0.0001) but not haemorrhagic stroke (n=2,470; OR 0.90, 95% CI=0.73-1.10; p=0.300). Significance was lost for ischaemic stroke in both young adults (18-60yr) (n=1,746; OR 1.26, 95% CI=0.97-1.65; p=0.09) and children (n=334; OR 1.24, 95% CI=0.74-2.08; p=0.41). Significant heterogeneity was observed for total (I2=60.1; p=0.0001) and ischaemic (I2=60.6; p=0.0003) stroke. Significance was lost for total stroke when analysed using a random-effect model (OR 1.15, 95% CI=0.99-1.34; p=0.06), but persisted in the ischaemic stroke sub-group (OR 1.23, 95% CI=1.03-1.46; p=0.02). Egger’s regression test suggested a low probability of publication bias (p>0.1 for all groups). Conclusions: This meta-analysis supports the carriage of the PlA2 allele of Glycoprotein IIIa as a risk factor for ischaemic stroke in adults. The totality of published data does not enable sub-group analyses based on sex, ethnicity or traditional cardiovascular risk factors, and so the need for further studies remains.

Daniel Petrovič - One of the best experts on this subject based on the ideXlab platform.

  • The a1/a2 polymorphism of the Glycoprotein IIIa gene and myocardial infarction in Caucasians with type 2 diabetes
    Molecular Biology Reports, 2013
    Co-Authors: Jovana Nikolajević-starčević, Daniel Petrovič
    Abstract:

    A PlA1/A2 polymorphism of Glycoprotein IIIa is known to be involved in the pathogenesis of coronary artery disease (CAD) and myocardial infarction (MI). The aim of this study was to investigate an association between the PlA1/A2 polymorphism of the Glycoprotein IIIa gene and the risk of MI in Caucasians with type 2 diabetes. 549 Caucasians with type 2 diabetes were enrolled in the cross sectional retrospective case–control study: 224 patients with MI and 325 diabetic subjects without CAD. Blood biochemical analysis was performed. The polymerase chain reaction with restriction fragment length polymorphism was used for genetic analysis. Patients with MI were older (62 ± 11.8 vs. 58.5 ± 11.6 years; P  

  • The a1/a2 polymorphism of the Glycoprotein IIIa gene and myocardial infarction in Caucasians with type 2 diabetes
    Molecular biology reports, 2012
    Co-Authors: Jovana Nikolajević-starčević, Daniel Petrovič
    Abstract:

    A PlA1/A2 polymorphism of Glycoprotein IIIa is known to be involved in the pathogenesis of coronary artery disease (CAD) and myocardial infarction (MI). The aim of this study was to investigate an association between the PlA1/A2 polymorphism of the Glycoprotein IIIa gene and the risk of MI in Caucasians with type 2 diabetes. 549 Caucasians with type 2 diabetes were enrolled in the cross sectional retrospective case–control study: 224 patients with MI and 325 diabetic subjects without CAD. Blood biochemical analysis was performed. The polymerase chain reaction with restriction fragment length polymorphism was used for genetic analysis. Patients with MI were older (62 ± 11.8 vs. 58.5 ± 11.6 years; P < 0.001), and had a longer duration of type 2 diabetes (17.6 ± 8.9 vs. 15.1 ± 9.2; P = 0.01) compared to the diabetics without CAD. A significant difference in distribution of the A2A2 genotype of Glycoprotein IIIa was not found between 224 diabetic patients with MI in comparison to 325 diabetics without CAD (11.6 vs. 14,1 %; n.s.). The diabetes duration and male sex were independent factors for the development of MI, whereas the PlA1/A2 polymorphism of Glycoprotein IIIa was not. To conclude, The A2A2 genotype of the Glycoprotein IIIa polymorphism was not associated with MI risk in Caucasians with type 2 diabetes.

  • A1/A2 polymorphism of the Glycoprotein IIIa gene and diabetic retinopathy in Caucasians with type 2 diabetes
    Clinical & experimental ophthalmology, 2011
    Co-Authors: Jovana Nikolajević-starčević, Mojca Globočnik Petrovič, Daniel Petrovič
    Abstract:

    Background:  A PlA1/A2 polymorphism of Glycoprotein IIIa is known to be involved in the pathogenesis of arterial thrombosis, myocardial infarction, stroke and type 2 diabetes, but there is no evidence of association with diabetic retinopathy. The aim of this study was to examine the role of the PlA1/A2 polymorphism of the Glycoprotein IIIa gene in the development of diabetic retinopathy in Caucasians with type 2 diabetes. Design:  Cross-sectional case–control study. Participants:  Totally 222 patients with diabetic retinopathy and 120 diabetic subjects without clinical signs of diabetic retinopathy from the Eye Clinic, University Medical Centre Ljubljana were enrolled in the study. Methods:  Fundus examination and blood biochemical analysis were performed. The polymerase chain reaction and restriction fragment length polymorphism were used. Main Outcome Measures:  The total cholesterol, triglyceride, high-density lipoprotein levels, fasting blood glucose and HbA1c were measured, and the genotypes of the PlA1/A2 polymorphism were determined. Results:  Patients with diabetic retinopathy had earlier onset, longer duration of type 2 diabetes and a higher incidence of insulin therapy compared to the diabetic patients without diabetic retinopathy. A significantly lower frequency of the A2A2 genotype of Glycoprotein IIIa was found in diabetic patients with retinopathy compared to those without retinopathy (odds ratio = 0.49, 95% confidence interval = 0.28–0.89; P = 0.018). Conclusions:  The A2A2 genotype of the Glycoprotein IIIa polymorphism was associated with lower risk for diabetic retinopathy in Caucasians with type 2 diabetes. Further studies are needed to elucidate its protective role in the development of diabetic retinopathy in Caucasians.

Christopher N. Floyd - One of the best experts on this subject based on the ideXlab platform.

  • Increased platelet expression of Glycoprotein IIIa following aspirin treatment in aspirin-resistant but not aspirin-sensitive subjects.
    British journal of clinical pharmacology, 2014
    Co-Authors: Christopher N. Floyd, Timothy Goodman, Silke Becker, Nan Chen, Agnesa Mustafa, Emma Schofield, James Campbell, Malcolm Ward, Pankaj Sharma, Albert Ferro
    Abstract:

    Aims Aspirin is widely used as an anti-platelet agent for cardiovascular prophylaxis. Despite aspirin treatment, many patients experience recurrent thrombotic events, and aspirin resistance may contribute to this. We examined the prevalence of aspirin resistance in a healthy population, and investigated whether the platelet proteome differed in aspirin-resistant subjects. Methods Ninety-three healthy subjects received aspirin 300 mg daily for 28 days. Before and at the end of treatment, urine was taken to determine 11-dehydrothromboxane B2, and blood was taken to measure arachidonic acid (AA)-induced aggregation of platelet-rich plasma and to interrogate the platelet proteome by mass spectrometric analysis with further confirmation of findings using Western blotting. Results In two of the 93 subjects, neither AA-induced aggregation nor urinary 11-dehydrothromboxane B2 was effectively suppressed by aspirin, despite measurable plasma salicylate concentrations, suggesting the presence of true aspirin resistance. Despite no detectable differences in the platelet proteome at baseline, following aspirin a marked increase was seen in platelet Glycoprotein IIIa expression in the aspirin-resistant but not aspirin-sensitive subjects. An increase in platelet Glycoprotein IIIa expression with aspirin resistance was confirmed in a separate cohort of 17 patients with stable coronary artery disease on long term aspirin treatment, four of whom exhibited aspirin resistance. Conclusions In a healthy population, true aspirin resistance is uncommon but exists. Resistance is associated with an increase in platelet Glycoprotein IIIa expression in response to aspirin. These data shed new light on the mechanism of aspirin resistance, and provide the potential to identify aspirin-resistant subjects using a novel biomarker.

  • The PlA1/A2 polymorphism of Glycoprotein IIIa as a risk factor for myocardial infarction: a meta-analysis.
    PloS one, 2014
    Co-Authors: Christopher N. Floyd, Agnesa Mustafa, Albert Ferro
    Abstract:

    Background The PlA2 polymorphism of Glycoprotein IIIa (GPIIIa) has been previously identified as being associated with myocardial infarction (MI), but whether this represents a true association is entirely unclear due to differences in findings from different studies. We performed a meta-analysis to evaluate whether this polymorphism is a risk factor for MI. Methods Electronic databases (MEDLINE and EMBASE) were searched for all articles evaluating genetic polymorphisms of GPIIIa. For studies where acute coronary events were recorded in association with genetic analysis, pooled odds ratios (ORs) were calculated using fixed-effects and random-effects models. The primary outcome measure was MI, and a secondary analysis was also performed for acute coronary syndromes (ACS) more generally. Findings 57 studies were eligible for statistical analysis and included 17,911 cases and 24,584 controls. Carriage of the PlA2 allele was significantly associated with MI (n = 40,692; OR 1.077, 95% CI 1.024–1.132; p = 0.004) but with significant publication bias (p = 0.040). The degree of association with MI increased with decreasing age of subjects (≤45 years old: n = 9,547; OR 1.205, 95% CI 1.067–1.360; p = 0.003) and with adjustment of data for conventional cardiovascular risk factors (n = 12,001; OR 1.240, 95% CI 1.117–1.376; p

  • The PlA1/A2 polymorphism of Glycoprotein IIIa as a risk factor for stroke: a systematic review and meta-analysis.
    PloS one, 2014
    Co-Authors: Christopher N. Floyd, Ben H Ellis, Albert Ferro
    Abstract:

    Background The PlA1/A2 polymorphism of Glycoprotein IIIa (GPIIIa) has been reported to be associated with risk of stroke in some studies, although other studies suggest no such association. This meta-analysis and systematic review was conducted to investigate the hypothesis that carriage of the PlA2 allele is a risk factor for stroke. Methods Electronic databases (MEDLINE and EMBASE) were searched for all articles evaluating carriage of the PlA2 allele and the incidence of stroke. Pooled odds ratios (ORs) were calculated using fixed-effect and random-effect models. Findings A total of 35 articles were eligible for inclusion, of which 25 studies were suitable for statistical analysis. For carriage of the PlA2 allele, OR 1.12 (n = 11,873; 95% CI = 1.03–1.22; p = 0.011) was observed for the incidence of stroke in adults, with subgroup analyses identifying the association driven by stroke of an ischaemic (n = 10,494; OR = 1.15, 95% CI = 1.05–1.27; p = 0.003) but not haemorrhagic aetiology (n = 2,470; OR = 0.90, 95% CI = 0.71–1.14; p = 0.398). This association with ischaemic stroke was strongest in individuals homozygous for the PlA2 allele compared to those homozygous for wild-type PlA1 (n = 5,906; OR = 1.74, 95% CI = 1.34–2.26; p 0.05). Conclusions The totality of published data supports the hypothesis that carriage of the PlA2 polymorphism of GPIIIa is a risk factor for ischaemic strokes, and specifically those of cardioembolic and large vessel origin.

  • The PlA1/A2 polymorphism of Glycoprotein IIIa in relation to efficacy of antiplatelet drugs: a systematic review and meta-analysis: The PlA1/A2 polymorphism and antiplatelet drug resistance
    British journal of clinical pharmacology, 2014
    Co-Authors: Christopher N. Floyd, Albert Ferro
    Abstract:

    Aim The PlA1/A2 polymorphism of Glycoprotein IIIa (GPIIIa) has been associated with both antiplatelet drug resistance and increased cardiovascular events. The aim of this study was to conduct the first meta-analysis investigating the association between carriage of the PlA2 allele and resistance to currently licensed antiplatelet drugs. Methods Electronic databases (MEDLINE and EMBASE) were searched for all articles evaluating genetic polymorphisms of GPIIIa. For studies where antiplatelet resistance was measured using validated techniques, pooled odds ratios (ORs) were calculated using fixed effects and random effects models. Results Sixteen studies were eligible for statistical analysis and included 1650 PlA1 homozygous subjects and 668 carriers of the PlA2 allele. For carriers of the PlA2 allele, OR 0.924 (n = 2318; 95% CI 0.743, 1.151; P = 0.481) was observed for resistance to any antiplatelet drug, OR 0.862 (n = 2085; 95% CI 0.685, 1.086; P = 0.208) for resistance to aspirin and OR 1.429 (n = 233; 95% CI 0.791, 2.582; P = 0.237) for resistance to clopidogrel. In the aspirin cohort, sub-group analysis revealed no statistical association in either healthy subjects or those with cardiovascular disease. PlA2 carriage was marginally associated with aspirin sensitivity using the fixed effects model when identified by the PFA-100 assay (n = 1151; OR 0.743, 95% CI 0.558, 0.989; P = 0.041) but with significant heterogeneity (I2 = 55%; P = 0.002). Significance was lost with analysis using a random effects model. Conclusions The totality of published data does not support an association between carriage of the PlA2 allele and antiplatelet drug resistance. Significant heterogeneity indicates the need for larger studies using validated and standardized assays.

  • Abstract W MP49: Carriage of the PlA2 Allele of Glycoprotein IIIa is Associated With an Increased Risk of Ischaemic Stroke: A Meta-Analysis
    Stroke, 2014
    Co-Authors: Ben H Ellis, Christopher N. Floyd, Albert Ferro
    Abstract:

    Introduction: The PlA1/A2 polymorphism of Glycoprotein IIIa has been associated with an increased risk of stroke, but with poor agreement between studies. Here we present a meta-analysis to assess the hypothesis that carriage of the PlA2 allele increases stroke risk. Methods: Electronic databases (MEDLINE and EMBASE) were searched for all articles evaluating carriage of the PlA2 allele and the incidence of stroke. Pooled odds ratios (ORs) were calculated using fixed-effect and random-effect models. Results: A total of 34 articles were eligible for statistical analysis (5,475 cases and 7,247 controls). For carriage of the PlA2 allele, OR 1.15 (n=12,115; 95% CI=1.05-1.26; p=0.002) was observed for total adult stroke, with sub-group analyses identifying an association with ischaemic (n=9,460; OR 1.22, 95% CI=1.10-1.35; p=0.0001) but not haemorrhagic stroke (n=2,470; OR 0.90, 95% CI=0.73-1.10; p=0.300). Significance was lost for ischaemic stroke in both young adults (18-60yr) (n=1,746; OR 1.26, 95% CI=0.97-1.65; p=0.09) and children (n=334; OR 1.24, 95% CI=0.74-2.08; p=0.41). Significant heterogeneity was observed for total (I2=60.1; p=0.0001) and ischaemic (I2=60.6; p=0.0003) stroke. Significance was lost for total stroke when analysed using a random-effect model (OR 1.15, 95% CI=0.99-1.34; p=0.06), but persisted in the ischaemic stroke sub-group (OR 1.23, 95% CI=1.03-1.46; p=0.02). Egger’s regression test suggested a low probability of publication bias (p>0.1 for all groups). Conclusions: This meta-analysis supports the carriage of the PlA2 allele of Glycoprotein IIIa as a risk factor for ischaemic stroke in adults. The totality of published data does not enable sub-group analyses based on sex, ethnicity or traditional cardiovascular risk factors, and so the need for further studies remains.

Jovana Nikolajević-starčević - One of the best experts on this subject based on the ideXlab platform.

  • The a1/a2 polymorphism of the Glycoprotein IIIa gene and myocardial infarction in Caucasians with type 2 diabetes
    Molecular Biology Reports, 2013
    Co-Authors: Jovana Nikolajević-starčević, Daniel Petrovič
    Abstract:

    A PlA1/A2 polymorphism of Glycoprotein IIIa is known to be involved in the pathogenesis of coronary artery disease (CAD) and myocardial infarction (MI). The aim of this study was to investigate an association between the PlA1/A2 polymorphism of the Glycoprotein IIIa gene and the risk of MI in Caucasians with type 2 diabetes. 549 Caucasians with type 2 diabetes were enrolled in the cross sectional retrospective case–control study: 224 patients with MI and 325 diabetic subjects without CAD. Blood biochemical analysis was performed. The polymerase chain reaction with restriction fragment length polymorphism was used for genetic analysis. Patients with MI were older (62 ± 11.8 vs. 58.5 ± 11.6 years; P  

  • The a1/a2 polymorphism of the Glycoprotein IIIa gene and myocardial infarction in Caucasians with type 2 diabetes
    Molecular biology reports, 2012
    Co-Authors: Jovana Nikolajević-starčević, Daniel Petrovič
    Abstract:

    A PlA1/A2 polymorphism of Glycoprotein IIIa is known to be involved in the pathogenesis of coronary artery disease (CAD) and myocardial infarction (MI). The aim of this study was to investigate an association between the PlA1/A2 polymorphism of the Glycoprotein IIIa gene and the risk of MI in Caucasians with type 2 diabetes. 549 Caucasians with type 2 diabetes were enrolled in the cross sectional retrospective case–control study: 224 patients with MI and 325 diabetic subjects without CAD. Blood biochemical analysis was performed. The polymerase chain reaction with restriction fragment length polymorphism was used for genetic analysis. Patients with MI were older (62 ± 11.8 vs. 58.5 ± 11.6 years; P < 0.001), and had a longer duration of type 2 diabetes (17.6 ± 8.9 vs. 15.1 ± 9.2; P = 0.01) compared to the diabetics without CAD. A significant difference in distribution of the A2A2 genotype of Glycoprotein IIIa was not found between 224 diabetic patients with MI in comparison to 325 diabetics without CAD (11.6 vs. 14,1 %; n.s.). The diabetes duration and male sex were independent factors for the development of MI, whereas the PlA1/A2 polymorphism of Glycoprotein IIIa was not. To conclude, The A2A2 genotype of the Glycoprotein IIIa polymorphism was not associated with MI risk in Caucasians with type 2 diabetes.

  • A1/A2 polymorphism of the Glycoprotein IIIa gene and diabetic retinopathy in Caucasians with type 2 diabetes
    Clinical & experimental ophthalmology, 2011
    Co-Authors: Jovana Nikolajević-starčević, Mojca Globočnik Petrovič, Daniel Petrovič
    Abstract:

    Background:  A PlA1/A2 polymorphism of Glycoprotein IIIa is known to be involved in the pathogenesis of arterial thrombosis, myocardial infarction, stroke and type 2 diabetes, but there is no evidence of association with diabetic retinopathy. The aim of this study was to examine the role of the PlA1/A2 polymorphism of the Glycoprotein IIIa gene in the development of diabetic retinopathy in Caucasians with type 2 diabetes. Design:  Cross-sectional case–control study. Participants:  Totally 222 patients with diabetic retinopathy and 120 diabetic subjects without clinical signs of diabetic retinopathy from the Eye Clinic, University Medical Centre Ljubljana were enrolled in the study. Methods:  Fundus examination and blood biochemical analysis were performed. The polymerase chain reaction and restriction fragment length polymorphism were used. Main Outcome Measures:  The total cholesterol, triglyceride, high-density lipoprotein levels, fasting blood glucose and HbA1c were measured, and the genotypes of the PlA1/A2 polymorphism were determined. Results:  Patients with diabetic retinopathy had earlier onset, longer duration of type 2 diabetes and a higher incidence of insulin therapy compared to the diabetic patients without diabetic retinopathy. A significantly lower frequency of the A2A2 genotype of Glycoprotein IIIa was found in diabetic patients with retinopathy compared to those without retinopathy (odds ratio = 0.49, 95% confidence interval = 0.28–0.89; P = 0.018). Conclusions:  The A2A2 genotype of the Glycoprotein IIIa polymorphism was associated with lower risk for diabetic retinopathy in Caucasians with type 2 diabetes. Further studies are needed to elucidate its protective role in the development of diabetic retinopathy in Caucasians.

Harrison W. Farber - One of the best experts on this subject based on the ideXlab platform.

  • Effect of hypoxia on endothelial cell surface Glycoprotein expression: modulation of Glycoprotein IIIa and other specific surface Glycoproteins.
    Experimental Cell Research, 1993
    Co-Authors: Gerald L. Weinhouse, Paula N. Belloni, Harrison W. Farber
    Abstract:

    Abstract Exposure to hypoxia alters many aspects of endothelial cell metabolism and function; however, changes in surface glycoconjugates under these conditions have not been extensively evaluated. In the current studies, we examined surface Glycoproteins of cultured bovine aortic (BAEC) and pulmonary arterial (BPAEC) endothelial cells under standard culture conditions (21% oxygen) and following exposure to hypoxia (0% oxygen) for varying time periods (30 min to 18 h) using a system of biotinylation, lectin binding (concanavalin A, Con A; Griffonia simplicifolia , GSA; Arachis hypogaea, PNA; Ricinus communis, RCA; or Triticum vulgaris, WGA), subsequent strep-avidin binding, and staining. Using these methods, we identified differences in lectin binding between the two cell types cultured in 21% oxygen with all lectins except PNA. With exposure to 0% oxygen, there was no change in lectin binding to most surface Glycoproteins. Several surface Glycoproteins, including Glycoprotein IIIa on both cell types, demonstrated a time-dependent decrease in lectin binding; in addition, there was an increase in lectin binding to a few specific surface Glycoproteins on each cell type within 30-60 min of exposure to 0% oxygen. These changes in specific surface Glycoproteins were confirmed in both cell types by 125I labeling. Increased lectin binding was observed for Con A binding BAEC Glycoproteins at molecular weight (MW) 116, 130, and 205 kDa, GSA binding BAEC Glycoproteins at MW 120 and 205 kDa, and RCA binding BPAEC Glycoproteins at MW 140 and 205 kDa. Increased binding of WGA or PNA was not observed during exposure to hypoxia. The specificity of lectin binding was further confirmed by competitive inhibition with the appropriate sugar. These studies demonstrate that there are baseline differences between BAEC and BPAEC cell surface Glycoproteins and that exposure to hypoxia is associated with little change in lectin binding to most surface Glycoproteins. There is, however, increased surface expression of a few Glycoproteins that differ depending of the origin of the endothelial cell. Although the mechanism of this increase in lectin binding is not yet clear, subsequent studies suggested that it is due to increased availability of select carbohydrate moieties. The time course of these alterations suggests a possible role in the endothelial cell response to decreases in ambient oxygen tension.