Genetic variation of platelet function and pharmacology: An update of current knowledge

Tobias Geisler; Elke Schaeffeler; Elke Schaeffeler; Meinrad Gawaz; Matthias Schwab

doi:10.1160/TH13-02-0145

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2013; 110(05): 876-887
DOI: 10.1160/TH13-02-0145

Theme Issue Article

Schattauer GmbH

Genetic variation of platelet function and pharmacology: An update of current knowledge

Tobias Geisler

¹Medizinische Klinik, Innere Medizin III, Kardiologie und Kreislauferkrankungen, Tübingen, Germany

,

Elke Schaeffeler

¹Medizinische Klinik, Innere Medizin III, Kardiologie und Kreislauferkrankungen, Tübingen, Germany

,

Elke Schaeffeler

¹Medizinische Klinik, Innere Medizin III, Kardiologie und Kreislauferkrankungen, Tübingen, Germany

,

Meinrad Gawaz

¹Medizinische Klinik, Innere Medizin III, Kardiologie und Kreislauferkrankungen, Tübingen, Germany

,

Matthias Schwab

¹Medizinische Klinik, Innere Medizin III, Kardiologie und Kreislauferkrankungen, Tübingen, Germany

› Author Affiliations

Abstract

Summary

Platelets are critically involved in atherosclerosis and acute thrombosis. The platelet phenotype shows a wide variability documented by the inherited difference of platelet reactivity, platelet volume and count and function of platelet surface receptors. Several candidate genes have been put into focus and investigated for their functional and prognostic role in healthy individuals and patients with cardiovascular (CV) disease treated with antiplatelet agents. In addition to genetic variation, other clinical, disease-related and demographic factors are important so-called non-genetic factors. Due to the small effect sizes of single nucleotide polymorphisms (SNP) in candidate genes and due to the low allele frequencies of functional relevant candidate SNPs, the identification of genetic risk factors with high predictive values generally depends on the sample size of study cohorts. In the post-genome era new array and bioinformatic technologies facilitate high throughput genome-wide association studies (GWAS) for the identification of novel candidate genes in large cardiovascular cohorts. One of the crucial aspects of platelet genomic studies is the precise definition of a specific clinical phenotype (e.g. stent thrombosis) as this will impact importantly the findings of genomic studies like GWAS. Here, we provide an update on genetic variation of platelet receptors and drug metabolising enzymes under specific consideration of data derived by GWAS. The potential impact of this information and the role in personalised therapeutic concepts will be discussed.

Keywords

Platelet physiology - platelet pharmacology - polymorphisms

Full Text

References

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