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

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<0.001). There was a low probability of publication bias for these subgroup analyses (all p<0.05). Conclusions: The 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.