The genetic architecture of blood pressure variation
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Corresponding author Patricia B. Munroe, PhD Clinical Pharmacology and The Genome Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, United Kingdom. E-mail: [email protected] Current Cardiovascular Risk Reports 2009, 3:418–425 Current Medicine Group LLC ISSN 1932-9520 Copyright © 2009 by Current Medicine Group LLC
High blood pressure affects over 1 billion people worldwide and is responsible for 50% of all cardiovascular deaths. Despite numerous candidate gene and linkage studies, no susceptibility loci for hypertension have been robustly validated except for rare monogenic disorders. Recent large meta-analyses of genome-wide association scans, however, have changed the situation. Thirteen new hypertension loci have now been described, many of which have strong biological candidates. All associated variants have common allele frequencies and exert modest to small effects on disease risk. Rare and low frequency variants with larger effect sizes in genes causing monogenic disorders have also been found, suggesting blood pressure heritability may be explained in part by a combination of both common and rare genetic variants. It is hoped these new findings will pave the way for a better understanding of blood pressure regulation and offer the potential to develop new treatments that may prevent heart disease and stroke.
Introduction The global burden of cardiovascular disease is continuing to rise, with simulations by the World Health Organisation suggesting the number of people with hypertension will exceed 1.5 billion by 2020 [1]. Recent estimates reveal that blood pressure (BP) plays an important part in 50% of the 17.5 million cardiovascular deaths that occur annually worldwide [1–3]. But even this high number disguises the true cost, as many more people live with but are disabled by cardiovascular disease. In spite of the development of multiple effective antihypertensive therapies that reduce stroke and heart attacks,
public health data from Western economies show hypertension remains poorly controlled. Indeed, only 10% to 25% of patients achieve current BP targets, and up to 20% of patients are resistant to current treatments [3,4]. This arises partly from the failure to apply existing effective measures but also from the need for a broader range of more effective therapies. Unfortunately, the discovery pipeline for new BP treatments within the pharmaceutical industry is the leanest it has been for 60 years. This is largely because most of the known physiologic systems implicated in BP regulation have been tested as therapeutic targets and have failed. Therefore, new approaches are needed to identify pathways that could offer new targets. This has led to the suggestion that an understanding of the genetic factors elevating BP might offer this possibility [4]. This review discusses the results of recent BP genetic studies and the significance and implications of these findings.
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