Platelet antigen 1/platelet antigen 2 polymorphism of glycoprotein IIIa as a risk factor for myocardial infarction: a meta-analysis

Abstract

BackgroundCarriage of the platelet antigen (PlA) 2 allele of glycoprotein IIIa (GPIIIa) has been previously identified as a potential risk factor for myocardial infarction. Whether this association is real remains unclear because agreement between study results since the first report in 1996 has been poor. The aim of this meta-analysis was to assess the strength of association between carriage of the PlA2 allele and myocardial infarction. MethodsMedline and Embase were searched up to and including April 1, 2013, for all articles evaluating genetic polymorphisms in the platelet GPIIIa receptor. For inclusion into the meta-analysis, studies must have reported the distribution of the PlA1/PlA2 genotype in relation to prevalence of myocardial infarction, either as raw data or as calculated odds ratios (ORs). Both case-control and cohort studies were considered, with familial-based studies and studies without an English translation excluded. Data were analysed with Comprehensive Meta-analysis software (version 2, Biostat, USA). Pooled ORs were calculated with fixed-effects and random-effects models, with 95% CIs to measure the strength of association. Tests for heterogeneity were done for each analysis, with significance set at p<0·05. For assessment of publication bias, we used a funnel plot and Egger's regression test. Findings51 studies were eligible for statistical analysis. They included 41 423 individuals, of whom 28 148 were homozygous for PlA1 and 11 900 were carriers of the PlA2 allele (raw genotype data were unavailable for 1375 individuals). Individuals carrying the PlA2 allele had a increased odds of myocardial infarction compared with people who did not carry the PlA2 allele (OR 1·083, 95% CI 1·029–1·140; p=0·002). Subgroup analysis of data adjusted for conventional cardiovascular risk factors where available (n=9330) showed an increased association between carriage of the PlA2 allele and myocardial infarction (OR 1·240, 95% CI 1·117–1·376; p<0·001). Further subgroup analyses revealed an increase in the association with decreasing age at the time of myocardial infarction (≤65 years, n=15 719, OR 1·097, 95% CI 1·005–1·197, p=0·038; ≤55 years, n=13 577, OR 1·140, 95% CI 1·032–1·258, p=0·010; and ≤45 years, n=6589, OR 1·198, 95% CI 1·059–1·355, p=0·004). Significant heterogeneity was observed for all analyses, with the use of the random-effects model maintaining a significant association between carriage of the PlA2 allele and myocardial infarction for all but the ≤65-year-old subgroup (OR 1·63, 95% CI 0·997–1·356; p=0·054). Egger's regression test was not significant for all analyses, suggesting low probability of publication bias. InterpretationThe totality of published data supports carriage of the PlA2 allele as a significant risk factor for myocardial infarction, with the strength of association greatest for younger people. This age-skewed risk profile is most likely explained by the effect of carriage of the allele being attenuated by the progression, and hence increased importance, of conventional cardiovascular risk factors with age. This hypothesis is supported by the subgroup analysis of data adjusted for cardiovascular risk factors, which showed an increased association compared with the main analysis. FundingGuy's and St Thomas' Charity.