Genetic and pharmacogenetic determinants of cardiovascular disease

Abstract

This thesis, titled __Genetic and pharmacogenetic determinants of cardiovascular disease__ is divided in three sections. In section one the genetic determinants of coronary restenosis are explored. In the first genome-wide association study on this condition, in the GENetic DEterminants of Restenosis study, we describe a novel locus on chromosome 12 possibly associated with restenosis. Furthermore, by using several analysis tools on this data, we describe multiple biological pathways and genes that are likely associated with restenosis. In section two, we focus on genetic factors involved in three other (cardio)vascular diseases. We explore the role of DNA repair genes in myocardial infarction and stroke and the genetic determinants of dialysis shunt failure. Section three is on pharmacogenetics. In particular, we were interested in genetic variation involved in aspirin and clopidogrel resistance. We validated two genetic polymorphisms associated with recurrent thrombotic events during treatment with these agents in patients with an acute myocardial infarction. Genetic research is a fast developing field of research. By increasing our knowledge on the molecular background of diseases, genetics potentially could lead to more personalized treatment in the near future.