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

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.

2016 European Guidelines on cardiovascular disease prevention in clinical practice

“…76,82,83 Recently, a genetic risk score based on 27 genetic variants enabled the identification of subjects at increased risk of CAD, who would benefit the most from statin therapy, even after adjustment for family history. 84 Still, it is likely that some reported associations might be due to chance, 85 and replication studies are needed to confirm positive findings. Currently, many commercial tests are available, allowing an almost complete assessment of an individual's genome, and strong pressure is being applied to use this information to predict genetic risk and to make genetic testing a routine measure.…”

2016 European Guidelines on cardiovascular disease prevention in clinical practice

“…Niedawno wykazano, że algorytm ryzyka genetycznego, oparty na 27 wariantach genetycznych, umożliwiał identyfikację osób z podwyższonym ryzykiem CAD, które mogłyby odnieść największą korzyść z włączenia statyny, nawet po wprowadzeniu poprawek dla wywiadu rodzinnego [84]. Prawdopodobnie niektóre obserwowane zależności mogą być dziełem przypadku [85]. Potrzebne są badania replikacyjne w celu potwierdzenia tych obserwacji.…”

Identification ofITGA2BandITGB3Single-Nucleotide Polymorphisms and Their Influences on the Platelet Function

“…The ITGA2B spanning 17 kb has 30 exons, whereas the ITGB3 spanning 46 kb has 15 exons; they are closely located on chromosome 17q21.32 without evidence for coordinated expression [5]. A few studies have linked single-nucleotide polymorphisms (SNPs) in ITGA2B and ITGB3 with increased or decreased platelet responses to various agonists and the risk of acute coronary syndrome and atherosclerosis [6–8]. …”