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Cardiovascular Genetics and Genomics for the Cardiologist CGA_A01.qxd 4/24/07 10:07 Page i Cardiovascular Genetics and Genomics for the Cardiologist EDITED BY Victor J. Dzau, MD James B. Duke Professor of Medicine Director, Mandel Center for Hypertension and Atherosclerosis Research Chancellor for Health Affairs Duke University Durham, NC, USA Choong-Chin Liew, PhD Professor Emeritus, Department of Laboratory Medicine and Pathobiology, University of Toronto Toronto Ontario, Canada and (formerly) Visiting Professor of Medicine Brigham and Women’s Hospital Harvard Medical School Boston, MA, USA CGA_A01.qxd 4/24/07 10:07 Page ii © 2007 by Blackwell Publishing Blackwell Futura is an imprint of Blackwell Publishing Blackwell Publishing, Inc., 350 Main Street, Malden, Massachusetts 02148-5020, USA Blackwell Publishing Ltd, 9600 Garsington Road, Oxford OX4 2DQ, UK Blackwell Science Asia Pty Ltd, 550 Swanston Street, Carlton, Victoria 3053, Australia All rights reserved. No part of this publication may be reproduced in any form or by any electronic or mechanical means, including information storage and retrieval systems, without permission in writing from the publisher, except by a reviewer who may quote brief passages in a review. First published 2007 1 2007 ISBN: 978-1-4051-3394-4 Library of Congress Cataloging-in-Publication Data Cardiovascular genetics and genomics for the cardiologist / edited by Victor J. Dzau, Choong-Chin Liew. p. ; cm. Includes bibliographical references and index. ISBN-13: 978-1-4051-3394-4 (alk. paper) ISBN-10: 1-4051-3394-5 (alk. paper) 1. Cardiovascular system–Diseases–Genetic aspects. 2. Cardiovascular system–Molecular aspects. 3. Genomics. I. Dzau, Victor J. II. Liew, Choong-Chin. [DNLM: 1. Cardiovascular Diseases–genetics. 2. Cardiovascular Diseases–therapy. 3. Genomics. WG 120 C26745 2007] RC669.C2854 2007 616.1′042–dc22 2007005634 A catalogue record for this title is available from the British Library Commissioning Editors: Steve Korn and Gina Almond Development Editors: Vicki Donald and Beckie Brand Editorial Assistant: Victoria Pittman Production Controller: Debbie Wyer Set in 9.5/12pt Minion by Graphicraft Limited, Hong Kong Printed and bound in Singapore by Fabulous Printers Pte Ltd For further information on Blackwell Publishing, visit our website: www.blackwellcardiology.com The publisher’s policy is to use permanent paper from mills that operate a sustainable forestry policy, and which has been manufactured from pulp processed using acid-free and elementary chlorine-free practices. Furthermore, the publisher ensures that the text paper and cover board used have met acceptable environmental accreditation standards. Blackwell Publishing makes no representation, express or implied, that the drug dosages in this book are correct. Readers must therefore always check that any product mentioned in this publication is used in accordance with the prescribing information prepared by the manufacturers. The author and the publishers do not accept responsibility or legal liability for any errors in the text or for the misuse or misapplication of material in this book. CGA_A01.qxd 4/24/07 10:07 Page iii Contents Contributors, v 7 Heart failure, 137 Markus Meyer, Peter VanBuren Foreword, vii 8 The implications of genes on the pathogenesis, Introduction, ix diagnosis and therapeutics of hypertension, 1 The gene in the twenty-first century, 1 166 Choong-Chin Liew, Victor J. Dzau Kiat Tsong Tan, Choong-Chin Liew Part I Cardiovascular single gene Part III Therapies and applications disorders 9 Gene therapy for cardiovascular disease: 2 Monogenic hypercholesterolemia, 19 inserting new genes, regulating the expression Ruth McPherson of native genes, and correcting genetic defects, 195 3 Hypertrophic cardiomyopathy, 30 Ion S. Jovin, Frank J. Giordano Ali J. Marian 10 Stem cell therapy for cardiovascular disease, 4 Dilated cardiomyopathy and other 225 cardiomyopathies, 55 Emerson C. Perin, Guilherme V. Silva Mitra Esfandiarei, Robert Yanagawa, Bruce M. McManus 11 Pharmacogenetics and personalized medicine, 250 5 The long QT syndrome, 83 Julie A. Johnson, Issam Zineh Sabina Kupershmidt, Kamilla Kelemen, Tadashi Nakajima 12 The potential of blood-based gene profiling for disease assessment, 277 Steve Mohr, Choong-Chin Liew Part II Cardiovascular polygenic Index, 301 disorders Colour plates are found facing p. 20 6 Atherosclerosis, 113 Päivi Pajukanta, Kiat Tsong Tan, Choong-Chin Liew iii CGA_A01.qxd 4/24/07 10:07 Page iv CGA_A01.qxd 4/24/07 10:07 Page v Contributors Victor J. Dzau, MD Ali J. Marian, MD Duke University Center for Cardiovascular Genetic Research Medical Center The Brown Foundation Institute of Molecular Medicine Durham, NC, USA The University of Texas Health Science Center Texas Heart Institute at St. Luke’s Episcopal Hospital Mitra Esfandiarei, PhD Houston, TX, USA James Hogg iCAPTURE Centre Providence Health Care Research Bruce M. McManus, MD, PhD, FRSC Institute UBC St. Paul’s Hospital The James Hogg iCAPTURE Centre for Cardiovascular and Vancouver, BC, Canada Pulmonary Research St. Paul’s Hospital/Providence Health Care Department of Pathology and Laboratory Medicine Frank J. Giordano, MD University of British Columbia Cardiovascular Gene Therapy Program Vancouver, BC, Canada Yale University School of Medicine New Haven, CT, USA Ruth McPherson, MD, PhD, FRCPC Departments of Medicine and Biochemistry Julie A. Johnson, PharmD University of Ottawa Heart Institute Departments of Pharmacy Practice and Medicine Ottawa, ON, Canada (Cardiovascular Medicine) Colleges of Pharmacy and Medicine, and Center for Markus Meyer, MD Pharmacogenomics Departments of Medicine and Molecular Physiology and University of Florida Biophysics Gainesville, FL, USA University of Vermont College of Medicine Ion S. Jovin, MD Burlington, VT, USA Cardiovascular Gene Therapy Program Yale University School of Medicine Steve Mohr, PhD New Haven, CT, USA GeneNews Corporation Toronto, ON, Canada Kamilla Kelemen, MD Tadashi Nakajima, MD, PhD Departments of Anesthesiology, and Division of Clinical Department of Anesthesiology Pharmacology Vanderbilt University School of Medicine Vanderbilt University School of Medicine Nashville, TN, USA Nashville, TN, USA Päivi Pajukanta, MD, PhD Sabina Kupershmidt, PhD Department of Human Genetics Assistant Professor David Geffen School of Medicine at UCLA Anesthesiology Research Divison Los Angeles, CA, USA Vanderbilt University Nashville, TN, USA Emerson C. Perin, MD, PhD New Cardiovascular Interventional Technology Choong-Chin Liew, PhD Texas Heart Institute GeneNewsCorporation Baylor Medical School Toronto, ON, Canada Houston, TX, USA v CGA_A01.qxd 4/24/07 10:07 Page vi vi Contributors Guilherme V. Silva, MD Robert Yanagawa, BSc, PhD Stem Cell Center The James Hogg iCAPTURE Centre for Cardiovascular and Texas Heart Institute Pulmonary Research Baylor Medical School St. Paul’s Hospital/Providence Health Care Houston, TX, USA Department of Pathology and Laboratory Medicine University of British Columbia Kiat Tsong Tan, MD, MRCP, FRCR Vancouver, BC, Canada Department of Radiology University of Bristol Issam Zineh, PharmD Bristol, UK Departments of Pharmacy Practice and Medicine (Cardiovascular Medicine) Peter VanBuren, MD Colleges of Pharmacy and Medicine, and Center for Departments of Medicine and Molecular Physiology and Pharmacogenomics Biophysics University of Florida University of Vermont Gainesville, FL, USA College of Medicine Burlington, VT, USA CGA_A01.qxd 4/24/07 10:07 Page vii Foreword In medicine, new developments seem to creep vascular conditions. With our genetic sequence along until they add up to a momentous shift, such known and these technologies available, however, as those created by the development of X-ray tech- researchers’ hunt for genetic factors underlying nology, the discovery of penicillin, or the advent of common, genetically complex diseases will be sig- open heart surgery. More recently, dramatic shifts nificantly accelerated. It is a natural extension that in clinical practice have stemmed from the devel- this research will bring new treatment, prevention opment of minimally invasive surgical techniques and diagnostic strategies to medicine. As a result, and the identification of lifestyle factors that signi- tomorrow’s medical graduates will be well-versed ficantly affect disease risk, particularly for heart dis- in genetics, and today’s practicing physicians will ease and diabetes. But perhaps no development of need to be as well. the last decade will prove more revolutionary to This book will allow cardiologists and others to medicine as we know it today than the completion “catch up” with the genetic revolution and to pre- of the Human Genome Project in 2003. This inter- pare for the impact the Human Genome Project national effort provided not just the sequence of will have on the practice of cardiovascular medi- our genetic building blocks, but a raft of new tech- cine. Get ready. Change is coming, and in many nologies and computational abilities that made the cases it’s already here. project possible. Peter Agre, MD, Nobel Laureate 2003 Research done “the old fashioned way” – without Vice Chancellor for Science and Technology the technologies of the Human Genome Project – Duke University Medical Center already has resulted in treatment advances that Durham, NC, USA target the genetic problems of “single-gene” cardio- vii CGA_A01.qxd 4/24/07 10:07 Page viii CGA_A01.qxd 4/24/07 10:07 Page ix Introduction Until recently, a modest knowledge of genetics has context. What is a gene? How did ideas about the been more than adequate
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