Genetics of Cardiomyopathy and Heart Failure, An Issue of Heart Failure Clinics

Calum Macrae

Description

This issue explores the genetic basis of specific cardiomyopathies and phenotypic components of heart failure with an eye to the clinical implications of this genetic knowledge. An understanding of the genetic causes of disease can aid in development of effective prevention and management strategies.

Sujets

• Médecine
• Spécialités médicales
• Medical
• Cardiology

Informations

• Publié par: Saunders
• Date de parution: 22 avril 2010
• Nombre de lectures: 2
• EAN13: 9781455700356
• Langue: English
• Poids de l'ouvrage: 3 Mo

Extrait

Heart Failure Clinics , Vol. 6, No. 2, April 2010
ISSN: 1551-7136
doi: 10.1016/S1551-7136(10)00007-3

Contributors
Heart Failure Clinics
Genetics of Cardiomyopathy and Heart Failure
Calum A. MacRae
Cardiovascular Division, Brigham and Women's Hospital, Thorn 11, 75 Francis Street, Boston, MA 02115, USA
ISSN  1551-7136
Volume 6 • Number 2 • April 2010

Contents
Cover
Contributors
Forthcoming Issues
Editorial
Preface
Genetics of Dilated Cardiomyopathy
Hypertrophic Cardiomyopathy
Arrhythmogenic Right Ventricular Cardiomyopathy
Genetics of Restrictive Cardiomyopathy
Atrial Fibrillation in Congestive Heart Failure
The Genetics of Conduction Disease
Heart Failure and Pulmonary Hypertension
The Genetics of Congestive Heart Failure
Clinical Screening and Genetic Testing
Genetics of Atrial Fibrillation
Genetic Basis of Ventricular Arrhythmias
Index
Heart Failure Clinics , Vol. 6, No. 2, April 2010
ISSN: 1551-7136
doi: 10.1016/S1551-7136(10)00009-7

Forthcoming Issues
Heart Failure Clinics , Vol. 6, No. 2, April 2010
ISSN: 1551-7136
doi: 10.1016/j.hfc.2010.01.001

Editorial
Unleashing Our Healthy Avatars Using Cardiovascular Genetics

Ragavendra R. Baliga, MD, MBA, FRCP, FACC, FRS (Med)
OSU Heart Center and Ross Heart Hospital, The Ohio State University Medical Center, Columbus, OH, USA
E-mail address: [e-mail]
E-mail address: [e-mail]

James B. Young, MD, FACC ,
Division of Medicine and Lerner College of Medicine, Cleveland Clinic, Cleveland, OH, USA
E-mail address: [e-mail]
E-mail address: [e-mail]


Ragavendra R. Baliga, MD, MBA, FRCP, FRS (Med) Consulting Editor

James B. Young, MD Consulting Editor
The field of genetics recently has witnessed quantum leaps of progress. In 1996, Megan and Morag, two lambs, were cloned from embryonic cells and the same team created Dolly the lamb from adult undifferentiated cells. 1 Subsequently mice, calves, piglets, kittens, horses, rats, and dogs all have been cloned ( Fig. 1 ). The push for personalized medicine (the ability to tailor medical care to an individual’s genes) also resulted in major efforts to better understand the human genetic make-up. These include the Human Genome Project, 2 The Single Nucleotide Polymorphism database, 3 the HapMap Project, 4, 5 the 1000 Genome Project, 6 and the Genome 10K Initiative. 7 The Human Genome Project was successfully completed in 2003 in that it identified all of the approximately 25,000 genes in the human DNA and determined the sequence of 3 billion chemical base pairs that make up the human DNA. The Single Nucleotide Polymorphism database and International HapMap Project (unveiled in 2005) aim to provide essential data for research into single nucleotide polymorphisms, which are markers of genetic diversity. By comparing these data with single nucleotide polymorphisms from patients with specific diseases, researchers hope to determine the genetic “glitches” that underlie those disorders.

Fig. 1 Cloning timeline.
From Wadman M. Cloning special: Dolly: a decade on. Nature 2007;445:800–11; with permission.
These innovative efforts have generated both political and ethical concerns. Several new regulatory measures have been announced to better harness these developments. On September 18, 2008, the US Food and Drug Administration published a document outlining how it proposes to regulate genetically engineered animals. 8 The proposed regulations effectively treat such animals as drugs to provide grounds for Food and Drug Administration oversight and control. The United States Senate outlawed genetic discrimination. 9 The Genetic Information Nondiscrimination Act bans the use of genetic information in hiring, firing, promotion, and compensation decisions, and prohibits collecting genetic information from employees by employers. This bill also prevents health plans and insurers from denying coverage or boosting premium prices based on a person’s genetic data, such as whether they have gene variants known to increase disease risk. It also forbids them from requesting or requiring people to take genetic tests. More recently, in November 2009, the United States government issued draft guidelines for how synthetic-biology companies should screen customers and their gene orders to protect against bioterrorism. Additionally, several for-profit companies offer relatively inexpensive and quick-to-report personal genomic characterization for anyone willing to send a cotton swab of their cheek along with a check to the laboratory.
In the interim a virtual map of the expression of 20,000 genes in the mouse brain was completed in 2006, 10 and the first data to map the spinal cord have been released. 11 When completed, the freely accessible atlas will chart the expression patterns of at least 18,500 genes throughout the spinal cord of juvenile and adult mice. Although similar strides have not yet been made with the cardiovascular system, Dr Calum MacRae, from Harvard Medical School, has assembled a world-class team of genetic specialists with an interest in the genetics of cardiomyopathy and heart failure. These diseases cannot always be attributed to mutations in a single gene or genetic pathway, and teasing out each genetic contribution from the tangled knot of environmental and genetic factors is challenging. Despite these barriers, in this issue of Heart Failure Clinics , these contributors have helped us better understand the rapidly changing and dynamic field of cardiovascular genetics. It is hoped that this understanding of cardiovascular genetics provides impetus for the development of more powerful and safer therapeutic agents that should be more effective while allowing for more accurate determination of dosages, better compliance, promotion of advanced screening of heart failure patients, and development of better preventive strategies 12 by figuring out how to unleash our healthy genetic avatars.

References

1. M. Wadman. Cloning special: Dolly: a decade on. Nature . 2007;445(7130):800-801.
2. J.D. McPherson, M. Marra, L. Hillier, et al. A physical map of the human genome. Nature . 2001;409(6822):934-941.
3. S.T. Sherry, M. Ward, K. Sirotkin. dbSNP-database for single nucleotide polymorphisms and other classes of minor genetic variation. Genome Res . 1999;9(8):677-679.
4. E.G. Phimister. Genomic cartography: presenting the HapMap. N Engl J Med . 2005;353(17):1766-1768.
5. G.A. Thorisson, A.V. Smith, L. Krishnan, et al. The International HapMap project web site. Genome Res . 2005;15(11):1592-1593.
6. B.M. Kuehn. 1000 Genomes Project promises closer look at variation in human genome. JAMA . 2008;300(23):2715.
7. Genome 10K Community of Scientists. Genome 10K: a proposal to obtain whole-genome sequence for 10,000 vertebrate species. J Hered . 2009;100(6):659-674.
8. J.P. Gluck, M.T. Holdsworth. FDA releases draft guidance on regulation of genetically engineered animals. Kennedy Inst Ethics J . 2008;18(4):393-402.
9. J.H. Tanne. US Senate outlaws genetic discrimination. BMJ . 2008;336(7652):1038.
10. E.S. Lein, M.J. Hawrylycz, N. Ao, et al. Genome-wide atlas of gene expression in the adult mouse brain. Nature . 2007;445(7124):168-176.
11. M. Wadman. Spinal cord revealed in free gene map. Nature . 2008;454(7203):373.
12. R.R. Baliga, J.B. Young. Pharmacogenomics transforming medicine to create a world of immortal Struldbruggs or even a Methuselah? So be it!. Heart Fail Clin . 2010;6(1):xi-xiii.
Heart Failure Clinics , Vol. 6, No. 2, April 2010
ISSN: 1551-7136
doi: 10.1016/j.hfc.2009.12.006

Preface

Calum A. MacRae, MD, PhD
Cardiovascular Division, Brigham and Women’s Hospital, Thorn 11, 75 Francis Street, Boston, MA 02115, USA
E-mail address: [e-mail]


Calum A. MacRae, MD, PhD Guest Editor
Heart failure remains the single most common cause of death in the developed world and is fast becoming a major problem in the developing world. Tremendous advances have been made over the last two decades in the treatment of the antecedent forms of heart disease, improving survival in the context of myocardial injury that would previously have been fatal, so that the prevalence of heart failure continues to increase. While progress has been made in the treatment of heart failure with substantial effects on morbidity and mortality, in many instances the progressive decline in function that accompanies the syndrome is only delayed. It is clear that new advances in the understanding of heart failure require much deeper insight into the earliest mechanisms underlying this complex syndrome, and in particular the pathophysiologic determinants of maladaptation as opposed to homeostatic compensation. In this effort genetics have already played a major role and will continue to do so.
Genetic studies of primary forms of heart failure have uncovered genes responsible for many of the key components of the final decompensated state. In this issue each of these relatively rare cardiomyopathies are reviewed with a focus on their contribution to heart failure pathophysiology at different levels. Perhaps the most obvious link between typical forms of acquired heart failure and is seen in dilated cardiomyopathy. Some of the genes underlying hypertrophic cardiomyopathy are now also recognized to cause dilated cardiomyopathy in certain contexts, and families exist in which these two apparently distinctive responses are seen in different individuals with the same genetic cause. Similar overlap syndromes exist between dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy, and between hypertrophic cardiomyopathy and inherited cases of restrictive physiology. In the first section of this issue each of these is discussed in turn by leading investigators in the field.
Recent epidemiologic data have identified links between several other cardiovascular pheno