title: Genetic variation of platelet function and pharmacology: an update of current knowledge.
abstract: 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.
authors.affiliation: Tobias Geisler, Medizinische Klinik, Innere Medizin III, Kardiologie und Kreislauferkrankungen, Otfried-Müller-Str. 10, 72076 Tübingen, Germany, Tel: +49 7071 29 83688, E-mail: tobias.geisler@med.uni-tuebingen.de.
authors.forename: T
authors.initials: T
authors.lastname: Geisler
authors.forename: E
authors.initials: E
authors.lastname: Schaeffeler
authors.forename: M
authors.initials: M
authors.lastname: Gawaz
authors.forename: M
authors.initials: M
authors.lastname: Schwab
mesh_terms: D000818:Animals; D054316:Biomarkers, Pharmacological / Q000378:metabolism; D001792:Blood Platelets / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D038981:Receptors, Collagen / Q000235:genetics* / Q000378:metabolism; D039341:Receptors, Fibrinogen / Q000235:genetics* / Q000378:metabolism; D058470:Receptors, Purinergic P2Y / Q000235:genetics* / Q000378:metabolism; D012306:Risk
chemical_list: D054316:Biomarkers, Pharmacological; D010975:Platelet Aggregation Inhibitors; D038981:Receptors, Collagen; D039341:Receptors, Fibrinogen; D058470:Receptors, Purinergic P2Y
keywords: Platelet physiology; platelet pharmacology; polymorphisms