A meta-analysis of studies on the association of the platelet P1A polymorphism of glycoprotein IIIa and risk of coronary heart disease

Deborah Burr, Hani Doss, Glen E. Cooke, Pascal Goldschmidt-Clermont

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

The p1A2 polymorphism of the glycoprotein IIIa subunit of the fibrinogen receptor (GPIIb-IIIa) has been reported by some studies to be associated with an increased risk of coronary thrombosis. Following the first paper on the subject in 1996, a large number of studies have investigated the relationship between this polymorphism and coronary thrombosis, either at the epidemiological or at the cellular and molecular levels. The cellular and molecular studies have shown in a consistent manner that this polymorphism increases platelet responsiveness. In contrast, epidemiological studies have generated inconsistent results regarding the clinical impact of p1A2. We consider 12 epidemiological studies that investigate the link between presence/absence of this polymorphism and presence/absence of coronary heart disease. Each is a case-control study that reports an odds ratio. The studies are not directly comparable because they differ greatly in their patient pools and also in the way the data are analysed. We present several meta-analyses of these 12 studies. The simplest one is based on a standard frequentist random effects model with a normal distribution for the study effects (the per-study population log-odds ratios). We also consider a Bayesian version of this model, with a diffuse prior for the mean and variance of the normal distribution of the study effects. The conclusions from both of these analyses is about the same, and is that there is evidence that the P1A2 polymorphism is associated with an increased risk of coronary heart disease. A look at the reported log-odds ratios across studies suggests that the study effects do not come from a symmetric distribution. For this reason, we also consider semi-parametric priors for the distribution of the study effects. These priors are specifically designed for this kind of meta-analysis, and are based on a certain class of mixtures of Dirichlet priors. They can be designed to concentrate most of their mass around the family of normal distributions, but still allow for any other distribution. The semi-parametric Bayesian model continues to give evidence of an association between the P1A2 polymorphism and the risk of coronary heart disease.

Original languageEnglish
Pages (from-to)1741-1760
Number of pages20
JournalStatistics in Medicine
Volume22
Issue number10
DOIs
StatePublished - May 30 2003
Externally publishedYes

Fingerprint

Coronary Heart Disease
Platelets
Glycoprotein
Normal Distribution
Polymorphism
Coronary Disease
Coronary Thrombosis
Meta-Analysis
Glycoproteins
Blood Platelets
Odds Ratio
Epidemiologic Studies
Fibrinogen Receptors
Thrombosis
Gaussian distribution
Case-Control Studies
Dirichlet Prior
Symmetric Distributions
Case-control Study
Random Effects Model

Keywords

  • Coronary heart disease
  • Dirichlet prior
  • Meta-analysis
  • Polymorphism
  • Semi-parametric Bayesian model

ASJC Scopus subject areas

  • Epidemiology

Cite this

A meta-analysis of studies on the association of the platelet P1A polymorphism of glycoprotein IIIa and risk of coronary heart disease. / Burr, Deborah; Doss, Hani; Cooke, Glen E.; Goldschmidt-Clermont, Pascal.

In: Statistics in Medicine, Vol. 22, No. 10, 30.05.2003, p. 1741-1760.

Research output: Contribution to journalArticle

Burr, Deborah ; Doss, Hani ; Cooke, Glen E. ; Goldschmidt-Clermont, Pascal. / A meta-analysis of studies on the association of the platelet P1A polymorphism of glycoprotein IIIa and risk of coronary heart disease. In: Statistics in Medicine. 2003 ; Vol. 22, No. 10. pp. 1741-1760.
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