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Heart disease: How DNA testing can help identify risk

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Most people are familiar with the fact that heart attacks are common in America, affecting nearly 735,000 people a year1. That’s an alarming number, so today we’re going to focus on a more positive one: 23, which represents a group of genes that can be used to find people who are at risk of having heart disease. Potentially, it can also help them avoid serious related health problems.
In 2013, the American College of Medical Genetics published an important list known as the ACMG 59. In it, you’ll find a series of genetic diseases that can potentially be prevented, or whose impact can be lessened, by taking proactive steps. Of the 59 genes on this list, 23 of them relate to various types of heart disease.
“Heart disease” is a broad term that describes many conditions where the heart stops working properly. Basically, the heart works by generating a rhythmic pulse of electricity which washes over the heart like a wave. As this electrical wave hits the heart’s muscle cells, it forces them to contract. Proteins within the muscle cells snap into action and generate a forceful contraction. This forceful wave of electrical contraction closes in on the hollow parts of the heart (known as the chambers). Blood resting inside the chambers is pushed out of the heart and into the attached blood vessels.


DNA testing may help determine next steps

Heart function is dependent on three key processes: The production of a coordinated wave of electricity, the contraction of muscle cells in response to that electrical wave, and the flow of blood into blood vessels. When one of these three processes stops working properly, heart disease can follow. Importantly, researchers have found that understanding which step in this process is causing heart disease can help determine what preventative steps should be taken.
Such is the case for many of the diseases covered in the ACMG 59. Here’s how they relate to the three key processes in the heart:

Electrical pulse disruption

Romano-Ward syndrome and catecholaminergic polymorphic ventricular tachycardia (CPVT) are conditions where changes in the DNA affect the heart’s electrical rhythm2,3. Conduction of electricity is dependent on the flow of calcium, sodium, and potassium ions into and out heart cells. In these conditions, changes in the DNA alter the proteins that regulate this process which results in an irregular electrical pulse and heartbeat. This limits the flow of blood to the rest of the body or, in the case of CPVT, causes an erratic flurry of heart beats that can develop into more severe symptoms.

Muscle cell contraction

Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are conditions where the heart loses the ability to either contract (DCM) or relax (HCM) as it normally would4-7. In both conditions, blood flow out of the heart is decreased. Over time, this can result in changes to the heart’s shape and significantly increased odds of experiencing a heart attack.


Heart disease is a little less scary with the right information

Researchers aiming to identify the cause of HCM and DCM found that about 25-60% of people with either condition have inherited changes to their DNA sequence that likely caused their disease. 12 of the 23 genes on the ACMG 59 list are known to cause HCM or DCM by altering the shape of contractile proteins in the heart muscle cells, resulting in disrupted muscle contraction4-7.
Similar to HCM and DCM, a condition known as arrhythmogenic right ventricular cardiomyopathy results in detrimental changes to the heart’s shape. In this condition, changes to the DNA weaken some of the connections between heart cells. With weaker connections, it’s easier for the cells to break apart. Like HCM and DCM, this type of heart disease can result in abnormal heartbeats and the potential sudden onset of a heart attack8,9.

Blocked blood flow

Finally, some of the 23 genes listed on the ACMG 59 are associated with a condition known as familial hypercholesterolemia (FH). Changes to these genes alter the bodies ability to clear cholesterol from the bloodstream which can then collect in the walls of blood vessels. With time, this begins to block the flow of blood and increases a person’s risk of heart attack10,11.
For each of these conditions, changes in the DNA sequence have been shown to be strongly linked to disease development. This means that DNA sequencing can be used to identify people who may be at increased odds of developing heart disease over the general population and who may benefit from preventative action.
Preventative action in heart disease depends on the specific condition a person has. For example, people who are likely to develop familial hypercholesterolemia may be able to avoid a serious heart attack by taking specific cholesterol lowering drugs and routinely checking in with a cardiologist10,11. Similarly, complications resulting from HCM, DCM, and certain other conditions may be avoided through a combination of targeted therapeutics, lifestyle changes, preventative surgery, and routine monitoring with healthcare professionals. In each case, early identification of individuals who are predisposed to heart disease is an important step towards helping them avoid potentially life threatening situations.
It’s true that heart disease is a scary topic, but it can be a little less scary with the right information and the right support network, including genetic counseling.
Helix will soon offer a product from PerkinElmer Genomics that tests for variants found in the ACMG 59 list. Click here to learn more about the ACMG 59 list and to sign up to learn when the PerkinElmer Genomics product is available.

1“Heart Disease.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 28 Nov. 2017,
2Alders, Mariëlle. “Long QT Syndrome.” Advances in Pediatrics., U.S. National Library of Medicine, 8 Feb. 2018,
3Napolitano, Carlo. “Catecholaminergic Polymorphic Ventricular Tachycardia.” Advances in Pediatrics., U.S. National Library of Medicine, 13 Oct. 2016,
4Cirino, Allison L. “Hypertrophic Cardiomyopathy Overview.” Advances in Pediatrics., U.S. National Library of Medicine, 16 Jan. 2014,
5Garfinkel, A C, et al. “Genetic Pathogenesis of Hypertrophic and Dilated Cardiomyopathy.” Advances in Pediatrics., U.S. National Library of Medicine, Apr. 2018,
6McNally, Elizabeth M., Jessica R. Golbus, and Megan J. Puckelwartz. “Genetic Mutations and Mechanisms in Dilated Cardiomyopathy.” The Journal of Clinical Investigation 123.1 (2013): 19–26. PMC. Web. 22 Aug. 2018.
7Hershberger, Ray E. “Dilated Cardiomyopathy Overview.” Advances in Pediatrics., U.S. National Library of Medicine, 23 Aug. 2018,
8McNally, Elizabeth. “Arrhythmogenic Right Ventricular Cardiomyopathy.” Advances in Pediatrics., U.S. National Library of Medicine, 25 May 2017,
9Corrado, Domenico et al. “Treatment of Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia: An International Task Force Consensus Statement.” Circulation 132.5 (2015): 441–453. PMC. Web. 22 Aug. 2018.
10Youngblom, Emily. “Familial Hypercholesterolemia.” Advances in Pediatrics., U.S. National Library of Medicine, 8 Dec. 2016,
11Bouhairie, Victoria Enchia, and Anne Carol Goldberg. “Familial Hypercholesterolemia.” Cardiology clinics 33.2 (2015): 169–179. PMC. Web. 22 Aug. 2018.
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