Cardiovascular Genetics and Genomics for the Cardiologist
Victor J. Dzau, Choong-Chin Liew, eds
308 pages. Oxford, UK: Blackwell Publishing, Inc; 2007. $149.95. ISBN 1-4051-3394-5
The power of Mendelian genetics to address the complexity of cardiovascular biology has been apparent since pioneering work unraveled the causes of hypertrophic cardiomyopathy and the long-QT syndrome. With the completion of the Human Genome Project, an increasing number of novel unbiased technologies have emerged, including expression profiling, proteomics, and metabolomics. As genetic and genomic techniques begin to enter translational research and even clinical practice, it is becoming increasingly important for cardiologists to be aware of the unique capabilities and limitations of these approaches to understanding disease. The recent wave of genome-wide association studies and the burgeoning field of regenerative medicine have not only emphasized the need for fluency in the language of modern biology, but also have highlighted a need for a major investment in patient-oriented research as investigators grapple with developing new phenotypes and evaluating innovative potential therapies. Implicit is a need for many more cardiologists trained to work at the translational interface with postgenomic techniques. It is physicians at this interface who are the principal target readership for Cardiovascular Genetics and Genomics for the Cardiologist. This multiauthored text, edited by C.C. Liew and Victor Dzau, aims to bring the practicing cardiologist up to speed in genetics, genomics, and their diagnostic or therapeutic applications within 300 pages. The authors and editors have in large measure succeeded, despite the breadth of the task in hand. The 12 relatively short chapters are organized into 3 sections dealing in sequence with single-gene disorders, polygenic syndromes, and therapies or applications.
The initial section provides 4 excellent chapters on the major Mendelian cardiac syndromes: familial hypercholesterolemia, hypertrophic cardiomyopathies, dilated cardiomyopathies, and the long-QT syndromes. The authors and editors have struck a fine balance between detail and scope, with any redundancy carefully harnessed for the benefit of the readership. Each chapter in this section not only neatly summarizes the fundamental genetics required to understand the topic but also conveys the implications for clinical management and the relevant insights into more common cardiac diseases. If there is one minor deficiency, it is the absence of a cohesive approach to genetic testing for such Mendelian diseases. The various hurdles encountered in the genetic diagnosis of conditions characterized by enormous effect sizes would be instructive for workers beginning to explore genetic insights in much less heritable disorders.
The second section explores several polygenic cardiovascular syndromes, specifically atherosclerosis, heart failure, and hypertension. Perhaps because of the complexity of these syndromes, these 3 chapters are considerably less focused on the specific details of the genetics or genomics of the respective conditions. The emphasis, particularly in the first 2 chapters of the section, is largely on the pathways that have already been implicated in each syndrome and on potential approaches that might be used to understand the genetics. This section unfortunately went to press before the emergence of the first rigorous genome-wide association studies, and as a result the insights from the early successes and failures of this approach are not included. Nevertheless, the expanding role of functional genomics in defining novel phenotypes is touched on throughout the section, and the major obstacles in applying genetics to common diseases are discussed.
The final section covers potential therapeutic or diagnostic uses of genetics and genomics in 4 chapters. These chapters each offer an excellent perspective on the chosen areas of interest: gene therapy, stem cell therapy, pharmacogenetics, and clinical expression profiling. The focus is on outlining the possibilities, reviewing work to date, and importantly, on defining the milestones that will have to be achieved if these strategies are to reach routine clinical practice. These chapters succeed in building a solid foundation from which the reader can move efficiently into the cited literature and offer the interested clinician a rapid entre into translational therapeutics. This section also succinctly defines the immense promise of genetics and genomics for diagnostic and prognostic applications long before mechanistic understanding has emerged.
In any fast-moving field, a text inevitably will omit some key developments, and future editions of this text will undoubtedly have to do justice to topics such as microRNAs, other noncoding regulatory transcripts, and genome-wide association studies, as well as potential technologies for investigating the downstream biology of multiple genes in parallel. Overall, this book accomplishes the goals it has set, providing an excellent initiation in genetics and genomics for the cardiologist or trainee who is beginning to explore the utility of these techniques for clinical or translational research. It offers a broad perspective on the utility of genetics and genomics in cardiology, with careful editing and outstanding referencing to balance the loss of detail intrinsic to a work of this scope.