Abstract
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.
Highlights
The fibrinogen receptor is the most abundant integrin on the platelet surface [1], and through binding a combination of fibrinogen, von Willebrand factor and fibronectin, its main function is to terminate haemorrhage following vascular injury
The presence of significant publication bias makes it unclear whether the association between carriage of the PlA2 allele and myocardial infarction (MI) is true for the total population studied
Analysis of the association between carriage of the PlA2 allele and MI using data adjusted for age, sex, ethnicity and cardiovascular risk factors demonstrated an increased level of association (n = 12,001; odds ratios (ORs) 1.240, 95% CI 1.117–1.376; p, 0.001) [87,88,96,97,101,109,110,112,119,120,121,125,127]
Summary
The fibrinogen receptor is the most abundant integrin on the platelet surface [1], and through binding a combination of fibrinogen, von Willebrand factor and fibronectin, its main function is to terminate haemorrhage following vascular injury. Despite this important physiological function, it plays a pathological role when stimulated excessively or inappropriately, and is a principal mediator of acute coronary thrombosis [2]. 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
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