Gene Polymorphisms and Signaling Defects
Understanding heritability of cardiovascular risk is a key issue in preventive medicine and of particular importance for the development of cost-efficient strategies to preserve cardiovascular health. Recent progress in genotyping technologies enabled det
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Gene Polymorphisms and Signaling Defects Christine Mannhalter, Michael Poteser, and Klaus Groschner
Abstract
Understanding heritability of cardiovascular risk is a key issue in preventive medicine and of particular importance for the development of cost-efficient strategies to preserve cardiovascular health. Recent progress in genotyping technologies enabled detailed insight into human genetic variability. Linkage analysis and genome-wide association screens have complemented candidate gene studies to uncover a large array of genetic variations associated with cardiovascular pathologies. For the majority of identified gene polymorphisms, the clinical impact is as yet unclear and the available information is still of limited value for cardiovascular risk prediction. However, genetic discoveries have greatly improved our understanding of pathophysiological principles. The identification of novel molecular players and target structures contributed significantly to therapeutic progress. In this chapter we aim to present an overview on polymorphisms in genes with proven or at least convincingly suggested causal relation to secondary risk factors and/or cardiovascular phenotypes. Special attention will be paid to functional consequences of genetic variations. Many of the polymorphisms that are causally involved in the pathogenesis of cardiovascular dysfunction impair cellular signaling processes and may in turn affect regulatory genetic networks. Unraveling of molecular mechanisms that link genetic variability to pathological phenotypes is still at a rather early stage. We will present here a selection of these mechanisms and discuss their clinical significance.
C. Mannhalter (*) Department of Laboratory Medicine, Medical University of Vienna, Währinger Gürtel 18-20, Vienna A-1090, Austria e-mail: [email protected] M. Poteser • K. Groschner Center for Physiological Medicine, Institute of Biophysics, Medical University of Graz, Harrachgasse 21/4, Graz A-8010, Austria e-mail: [email protected] I. Wakabayashi, K. Groschner (eds.), Interdisciplinary Concepts in Cardiovascular Health, DOI 10.1007/978-3-7091-1334-9_4, © Springer-Verlag Wien 2013
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Keywords
SNPs • Hypertension • Diabetes • Obesity • Dyslipidemia • Electrical remodeling • Hemostatic disorders
4.1
Introduction
Cardiovascular events represent highly complex pathological phenotypes that are for a large part determined by genetic predisposition. The availability of large-scale genotyping technologies has enabled genome-wide association studies (GWAS) that generated a large body of information on the genomics of cardiovascular disease. This allowed the identification of single-nucleotide polymorphisms (SNPs) in novel gene loci associated with cardiovascular diseases and phenotypes. Thus, GWAS approaches have considerably expanded our knowledge on the molecular players in cardiovascular pathophysiology. Albeit most of the unraveled associations reside outside of coding regions and/or in genomic regio
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