Platelet pharmacogenomics.
Platelet responsiveness to conventional antiplatelet therapy underlies a high interindividual variability influenced by various factors. For instance, antiplatelet therapy does not curtail the expected effects in a relevant number of patients as demonstrated by the occurrence of repeated cardiovascular events including stent thrombosis and/or by inadequate platelet inhibition measured by in vitro platelet function assays. Besides non-genetic factors such as age, gender, liver and renal function and co-medication, considerable variation of antiplatelet drug responsiveness can be attributed to genetic factors including polymorphisms and genetic variants of platelet surface proteins and drug metabolizing enzymes. Nowadays, platelet pharmacogenomics has started a new field with the goal to link genetic information of various drug targets to interindividual variability of drug response. Evolving data from large cohort studies suggest a promising role for pharmacogenomics in the context of antiplatelet therapy. Additionally, with the revolution of low cost and high-throughput genotyping techniques, genetic testing has become affordable for clinical application and individualization of therapy. However, a key issue to define the future role of pharmacogenomics will rely on the benefit and the timeliness of implementing the genetic information into therapeutic decision. Hence, it warrants further investigations to document the prognostic effects of therapeutic alterations in distinct genotypes. Concerning the safety profile of emerging antiplatelet and antithrombotic drugs in certain risk groups it would be fatal to individualize treatment barely on behalf of an atherothrombotic genotype. In contrast, individual risk assessment combining non-genetic information and pharmacogenetic analysis represents a reasonable concept. Here, we provide a review on current data describing the role of pharmacogenomics in the field of antiplatelet drug treatment in cardiovascular patients with future directions.
Medizinische Klinik, Abteilung Kardiologie und Kreislauferkrankungen, University Hospital Tuebingen, Tuebingen, Germany. christine.zuern@med.uni-tuebingen.de
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Zuern
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Schwab
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Gawaz
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Geisler
D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism*; D000077144:Clopidogrel; D015331:Cohort Studies; D023281:Genomics; D006801:Humans; D010597:Pharmacogenetics; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000494:pharmacology
D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin