Lack of relationship between the Pl<sup>A1</sup>/Pl<sup>A2</sup> polymorphism of platelet glycoprotein IIIa and premature myocardial infarction

Scaglione, L.; Bergerone, Serena; Gaschino, G.; Imazio, Massimo; Maccagnani, A.; Gambino, Roberto; Cassader, Maurizio; Leo, Margherita Di; Macchia, G.; Brusca, A; Pagano, G; Cavallo‐Perin, P.

doi:10.1046/j.1365-2362.1998.00298.x

Cited by 33 publications

(14 citation statements)

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“…Increased PIA2-prevalence in CAD and in patients after myocardial infarction was reported [31,32,33,34,35]. In a prospective nested case control trial within the Physician's Health Study no association was found of the PIA2-prevalence with any thrombotic endpoint at all and this was confirmed by the ECTIM and ARIC studies and by some smaller studies [36,37,38,39,40]. Others seem to resolve these striking differences by their suggestion that PIA2-prevalence does not act as a risk factor per se, but strongly determines the thrombogenic reactivity of the circulating platelets [32].…”

Section: Discussionmentioning

confidence: 88%

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: 88%

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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“…Further subgroup analysis based on comparison of the PlA1/A1 versus PlA2/A2 genotype failed to show a significant association ( n = 23,836; OR 1.023, 95% CI 0.877–1.192; p = 0.774) [70]–[72], [81], [82], [86]–[91], [95], [98]–[100], [102]–[104], [106]–[108], [111]–[114], [116], [117], [120], [122], [124], [128] (Figure 3); however, within this analysis, the number of subjects with the PlA2/A2 genotype was small, consisting of 333 cases and 1,504 controls.…”

Section: Resultsmentioning

confidence: 99%

“…Analysis of these studies revealed an association between carriage of the PlA2 allele and MI that was stronger than that seen in the primary analysis ( n = 18,349; OR 1.131, 95% CI 1.036–1.234; p = 0.006) [82], [84], [86], [87], [90], [101], [104], [107], [111], [117], [119]–[122], [124], [125].…”

Section: Resultsmentioning

confidence: 99%

The PlA1/A2 Polymorphism of Glycoprotein IIIa as a Risk Factor for Myocardial Infarction: A Meta-Analysis

2014

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BackgroundThe 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.MethodsElectronic 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.Findings57 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<0.001). There was a low probability of publication bias for these subgroup analyses (all p<0.05).ConclusionsThe presence of significant publication bias makes it unclear whether the association between carriage of the PlA2 allele and MI is true for the total population studied. However for younger subjects, the relative absence of conventional cardiovascular risk factors results in a significant association between carriage of the PlA2 allele and MI.

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“…An association between the presence of the HPA‐1b polymorphism and coronary thrombosis was first reported by Weiss et al (1996). In the numerous epidemiological studies that followed, this association was both supported (Carter et al , 1997; Walter et al , 1997; Abbate et al , 1998; Garcia‐Ribes et al , 1998; Gardemann et al , 1998; Pastinen et al , 1998; Zotz et al , 1998; Kastrati et al , 1999; Zotz et al , 2000) and challenged (Hato et al , 1997; Herrmann et al , 1997; Ridker et al , 1997; Samani & Lodwick, 1997; Durante‐Mangoni et al , 1998; Scaglione et al , 1998; Sperr et al , 1998; Cenarro et al , 1999; Kekomaki et al , 1999; Laule et al , 1999).…”

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confidence: 95%

The effect of human platelet alloantigen polymorphisms on the in vitro responsiveness to adrenaline and collagen

et al. 2001

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Summary. A number of clinical studies have suggested that carriage of the low frequency allele (b) of the human platelet antigen 1 (HPA-1) system is a risk factor for coronary thrombosis. We have examined the effect of a series of HPA biallelic polymorphisms (systems -1, -2, -3 and -5) on the in vitro platelet aggregation in response to adrenaline and collagen in 30 healthy volunteers. There was a significantly higher prevalence (10 out of 18) of carriers of the HPA-1b polymorphism among subjects showing a . 50% aggregation response to adrenaline (`responders') than the prevalence (1/12) in`non-responders' (P , 0´05). Platelets heterozygous for the HPA-1b polymorphism showed a significantly higher rate (slope) and greater extent (%) of adrenaline-induced aggregation than platelets not carrying the HPA-1b allele (P , 0´05). A greater extent of collageninduced aggregation was also demonstrated in HPA-1ab platelets (P , 0´05). Inhibition of adrenaline-induced aggregation following incubation with aspirin was greater (P , 0´01) in HPA-1ab than in HPA-1aa platelets. Collageninduced aggregation was slower in carriers of the HPA-5b allele than in HPA-5aa subjects (P , 0´05). Polymorphisms of the HPA-2 and HPA-3 systems were not associated with different aggregation responses to either adrenaline or collagen. These results support the clinical observation that polymorphism HPA-1b may predispose to increased platelet thrombogenicity and suggest that the presence of polymorphism HPA-5b might render the platelet less reactive to collagen.

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Lack of relationship between the Pl^A1/Pl^A2 polymorphism of platelet glycoprotein IIIa and premature myocardial infarction

Abstract: These results suggest that the P1A2 polymorphism of the platelet glycoprotein IIIa does not contribute to the genetic susceptibility to premature myocardial infarction.

Cited by 33 publications

References 14 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

The PlA1/A2 Polymorphism of Glycoprotein IIIa as a Risk Factor for Myocardial Infarction: A Meta-Analysis

The effect of human platelet alloantigen polymorphisms on the in vitro responsiveness to adrenaline and collagen

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Lack of relationship between the PlA1/PlA2 polymorphism of platelet glycoprotein IIIa and premature myocardial infarction

Abstract: These results suggest that the P1A2 polymorphism of the platelet glycoprotein IIIa does not contribute to the genetic susceptibility to premature myocardial infarction.

Cited by 33 publications

References 14 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

The PlA1/A2 Polymorphism of Glycoprotein IIIa as a Risk Factor for Myocardial Infarction: A Meta-Analysis

The effect of human platelet alloantigen polymorphisms on the in vitro responsiveness to adrenaline and collagen

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Lack of relationship between the Pl^A1/Pl^A2 polymorphism of platelet glycoprotein IIIa and premature myocardial infarction