Evaluation of an antibody‐based genotype classification of the platelet fibrinogen receptor (GPIIb/IIIa)

Schwippert‐Houtermans, B.; Strapatsakis, S.; Roesen, P.; Tschöepe, Diethelm

doi:10.1002/cyto.1133

Cited by 6 publications

(2 citation statements)

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“…Based on antibody binding data it is assumed that the PIA2-genotype is processed into functionally relevant phenotypical alterations of ligand (fibrinogen)-receptor (GPIIb-IIIa) interaction possibly causing hyperaggregation in response to stimulating agonists such as shear, matrix components or coagulation inducers [20,21,22,23,24]. Clearly, PIA2-carriers generate more thrombin after microvascular trauma which underlines the functional meaning of this particular platelet SNP also suggesting some pharmagenomic importance [25,26].…”

Section: Discussionmentioning

confidence: 99%

Genetic variation of the platelet- surface integrin GPIIb-IIIa ( PIA1/A2- SNP) shows a high association with Type 2 diabetes mellitus

et al. 2003

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Aims/hypothesis. The gene encoding the β 3 -subunit (GPIIIa) of the platelet α 2 β 3 -integrin (fibrinogen receptor) shows a polymorphism PlA1/A2 with the A2 allele putatively associated with an increased risk of acute ischaemic events. This study investigated whether Type 2 diabetes as a particular macrovascular risk factor associates with the thrombogenic PIA2 genotype. Methods. The PlA genotype was determined in 112 consecutive Type 2 diabetic patients additionally classified according to the presence of macrovascular disease. Forty-four non-diabetic patients with angiografically documented cardiovascular disease (CAD/ AMI) and a further 59 non-diabetic subjects with no angiografical signs of CAD were investigated as genomic background control (n=103). PIA-genotyping was carried out by standard restriction fragment length analysis (RFLA) of PCR amplified lymphocyte template DNA. Results. The overall allelic PlA2-prevalence accounted to 34.8% (39/112) in diabetic patients as compared to 14.6% (15/103) in non-diabetic patients [OR 3.1 (1.6-6.1), p<0.01].This odds ratio increased to 7.0 (2.5-19.7), (p<0.01) in subjects free of criteria of macrovascular disease. In non-diabetic control subjects without CAD there was an allelic PIA2 frequency of 10.2% (6/59) as compared to 20.5% (9/44) in patients with CAD and a history of AMI being less than either diabetes subgroup. The PIA2 prevalence in the subgroup of diabetes patients with macrovascular complications did not differ from the respective value in patients without macrovascular disease. [29.0% (20/69) vs. 44.2% (19/43)]. Conclusion/interpretation. This study confirms a trendwise association of PlA2 with severe coronary artery disease, but rather suggests an even stronger, highly significant association with the metabolic condition of Type 2 diabetes mellitus. This justifies the speculation that pathways dependent on the platelet α 2 β 3 integrin physiology could be implicated in the pathogenesis of Type 2 diabetes which lends further support to the "common soil" hypothesis of diabetes and vascular disease. [Diabetologia (2003) Abbreviations: AMI, acute myocardial infarction; CAD, coronary artery disease; GPIIIa, β 3 subunit of the platelet surface α 2 β 3 -integrin (GPIIb-IIIa, fibrinogen-receptor); PIA, platelet antigen; RGD, aminoacidsequence Arg-Gly-Asp; SNP, single nucleotide polymorphism. Diabetologia (2003) 46:984-989

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Section: Discussionmentioning

confidence: 99%

Genetic variation of the platelet- surface integrin GPIIb-IIIa ( PIA1/A2- SNP) shows a high association with Type 2 diabetes mellitus

et al. 2003

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“…Altogether 4,261 subjects participated in the baseline study (response 67%). Of those, 4,028 had been characterized according their PLA1A2 polymorphism by a flow cytometry based assay as described elsewhere [25] and could be included in the present analysis. Briefly, the polymorphism was determined from frozen EDTA cell samples by flow cytometry analysis using the stereospecific monoclonal antibody SZ21 directed against the ß3-subunit of the GPIIb/IIIa receptor.…”

Section: Introductionmentioning

confidence: 99%

PLA1A2 platelet polymorphism predicts mortality in prediabetic subjects of the population based KORA S4-Cohort

Stratmann

Meisinger

et al. 2014

Cardiovasc Diabetol

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ObjectiveThe genetic polymorphism concerning the ß3-subunit of platelet integrin receptor glycoprotein IIIa is held responsible for enhanced binding of adhesive proteins resulting in increased thrombogenic potential. Whether it is associated with mortality, HbA1c or platelet volume is tested prospectively in an epidemiological cohort.Research design and methodsPopulation-based Cooperative Health Research in the Region of Augsburg (KORA) S4-Survey (N = 4,028) was investigated for prognostic value of PLA1A2-polymorphism regarding all-cause mortality, correlation with HbA1c, and mean platelet volume. Multivariate analysis was performed to investigate association between genotype and key variables.ResultsPrevalence of thrombogenic allele variant PLA2 was 15.0%. Multivariate analysis revealed no association between PLA1A2 polymorphism and mortality in the KORA-cohort. HbA1c was a prognostic marker of mortality in non-diabetic persons resulting in J-shaped risk curve with dip at HbA1c = 5.5% (37 mmol/mol), confirming previous findings regarding aged KORA-S4 participants (55–75 years). PLA1A2 was significantly associated with elevated HbA1c levels in diabetic patients (N = 209) and reduced mean platelet volume in general population. In non-diabetic participants (N = 3,819), carriers of PLA2 allele variant presenting with HbA1c > 5.5% (37 mmol/mol) showed higher relative risk of mortality with increasing HbA1c.ConclusionPLA1A2 polymorphism is associated with mortality in participants with HbA1c ranging from 5.5% (37 mmol/mol) to 6.5% (48 mmol/mol). Maintenance of euglycemic control and antiplatelet therapy are therefore regarded as effective primary prevention in this group.

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Flow Cytometry

Carubbi¹,

Masselli²,

Vitale³

2017

Platelets in Thrombotic and Non-Thrombotic Disorders

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Evaluation of an antibody‐based genotype classification of the platelet fibrinogen receptor (GPIIb/IIIa)

Abstract: Platelet membrane glycoprotein (GP)IIb

Cited by 6 publications

References 50 publications

Genetic variation of the platelet- surface integrin GPIIb-IIIa ( PIA1/A2- SNP) shows a high association with Type 2 diabetes mellitus

Genetic variation of the platelet- surface integrin GPIIb-IIIa ( PIA1/A2- SNP) shows a high association with Type 2 diabetes mellitus

PLA1A2 platelet polymorphism predicts mortality in prediabetic subjects of the population based KORA S4-Cohort

Flow Cytometry

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