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GENETICS AND CARDIOVASCULAR PREVENTION: VARIATION TAKES CENTER STAGE.

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  2. GENETICS AND CARDIOVASCULAR PREVENTION: VARIATION TAKES CENTER STAGE.
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From Gregor Mendel's simplistic but brilliantly illuminating observations through the discovery of DNA and its emergence and description as the language of the genetic code, the growth of the field of molecular genetics has been arguably the greatest advance in biology over the past 100 years. The mapping of the human genome, a project once hailed as the singular key to opening the window on all of mankind's afflictions, has at the same time proven to be both more and less than expected. Among the current mysteries is why so much of the genome seems to be either redundant or does not code for product. The total number of base pairs is astoundingly large (on the order of 3 billion). It follows then that variability is a fundamental element in the human genetic condition. The variability revealed by recent analytical computational processes is far larger and more widely distributed than previously imagined. Until the past year or so, our genome-wide association studies have focused on the single nucleotide polymorphisms (SNPs) that are associated with symptoms or signs of disease. The recent finding that copy-number variation accounts for larger areas of the genome than previously suspected, making up 20% or more of individual genetic variability, has created a whole new area of investigation into the functional implications of this type of genetic variation.1

This “discovery” has been so extraordinary that Science named human genetic variation as the Science Breakthrough of the Year for 2007.2 What is the implication of this discovery for preventive cardiology? The answer comes to us from many sources. Even small variations in coding SNPs can influence clinical susceptibility to disease or response to its treatment. A sequence of articles recently published in the Journal of the American College of Cardiology utilizing data obtained from a large cohort study and several large clinical trials3–5 (WOSCOPS, CARE, and PROVE IT) all independently confirmed the important role of kinesin-like protein 6 (KIF6) Trp719Arg SNP polymorphism in conferring not only additional risk for coronary disease and myocardial infarction but also in predicting response to statin therapy. Prior identification of polymorphisms in the genes coding for many other cardiovascular products from ion channels to adrenergic receptors to angiotensin converting enzyme and left ventricular hypertrophy have highly specific implications for the management of cardiovascular risk. Even small variations may have enormous potential impact when magnified to the population level, a key tenet in Darwin's Origin of Species. But before you get your genome ”run,” be aware that the cost of this ultimate in personalized medicine is currently prohibitive (hundreds of thousands of dollars) and is not likely to yield immediately useful information. You can be sure, however, that the cost will come down and that the potential use of this tool has escaped neither government nor industry.

With the message emanating from Washington that the medicine of the future should be personalized and proactive, what could be better than to genetically personalize cardiovascular risk and its management to prevent illness? On the other hand, we need to have a health care system where genetics are not used to create heavier burdens for our people. We must assure, in fact, that an additional ”P” is added to those derived from the NIH view of the future of personalized medicine. That ”P” stands for privacy. The rights of the individual must be protected paramount to all other observations or inferences derived from their biological characteristics. Resources for the greater good of all must derive from the application of resources to the individual—a spin on Geoffrey Rose's classic concept of ”sick individuals and sick populations.”Not all risk is uniform. Much more research from both epidemiological studies and clinical trials will be necessary to determine the clinical importance of genetic risk determination, likely to be a highly complex and variable phenomenon. In addition, the role of nature vs nurture confounds the intervention process. Much of what we are learning about genetic variability relates to the interactions of genes and environment. We have barely begun to shed light on this vital area. Knowing the responses of individuals to therapeutic lifestyle change, including proper diet and exercise, will assume an even greater role in the future as costs of other preventive and treatment interventions continue to rise.

Over the course of the past 2 years, this column has offered me the wonderful opportunity to opine on matters relating to the American Society for Preventive Cardiology (ASPC) and the current state of affairs of preventive cardiology. I have been blessed by the first amendment and a benevolent editor in Ezra Amsterdam, who has given me free rein to espouse my ideas before our readership and (hopefully) beyond. As my term as President of ASPC winds down, it is appropriate to come full circle with respect to my initial message to you, entitled “The Past as Prologue.” My term has been one of transition. Many of you have gathered over the years at our annual dinner meetings, held in conjunction with the annual scientific meeting of the AHA Council on Epidemiology and Prevention. I have already used this space to give thanks to the leadership group whose initiative and foresight has moved the Society into a new era. Chief among those leaders has been Lori Mosca. Her extraordinary vision, enthusiasm, energy, and dedication to make something more of this society has provided me with the opportunity, support, and resources to make that happen. Even as we begin to grow in size and pursue our educational goals, transition continues.

Our society management, historically the burden of the clerical staff of the current President was over the past 2 years taken over by management through Le Jacq. For taking on this task, I personally have been truly grateful. T. Anthony Howell, then President of Le Jacq, deserves enormous kudos for shouldering the majority of the burden of chartering the society, helping establish its tax-exempt charitable status as a medical education entity, organizing our financial affairs, and upgrading the Web site (www.aspconline.org). As part of my recurring message to our readership and membership, I encourage you to make our society even more active in the years to come. Incoming president, Peter W. F. Wilson, is well known throughout the entire field of preventive cardiology. As former career investigator at Framingham and author of 4 books and hundreds of original papers, Peter brings a wealth of experience to his new role. He has been a colleague and personal friend of mine for nearly 35 years. I also welcome his energy and wit as he becomes our next president. Become a volunteer yourself and help assure our future success.

References

  1. Top of page
  2. GENETICS AND CARDIOVASCULAR PREVENTION: VARIATION TAKES CENTER STAGE.
  3. References