Cardiovascular Disease: Is It In Your Genes?

Cardiovascular disease (CVD) is a leading cause of death globally, but it’s not just your lifestyle that affects your heart health. Your genetic makeup also plays a significant role in determining whether you’re at risk for heart disease, often in combination with factors like diet, exercise, and environment. But just how much do our genes influence our risk? By exploring the genetic markers linked to CVD, we can gain insight into the complex relationship between our DNA and heart health.

How Genetics Influence Heart Disease

Genetics can shape many aspects of our health, and cardiovascular disease is no exception. Some individuals are more predisposed to CVD due to genetic mutations inherited from their parents. These mutations can affect various processes, including how the body manages cholesterol, blood vessel function, and cellular growth in blood vessels. In fact, genetics and lifestyle often work together to determine an individual’s overall risk for heart disease, highlighting the importance of both.¹

Advancements in genetic research have uncovered a number of key mutations that influence an individual’s risk of developing cardiovascular disease. Many of these genetic markers are involved in lipid metabolism and vascular health, making them essential targets for understanding and managing heart disease.^1,2 Let’s explore some of the major genes that have been linked to CVD risk.

Key Genes Linked to Cardiovascular Disease

Several genes play a central role in how cholesterol is processed and regulated in the body. Elevated cholesterol levels, especially low-density lipoprotein (LDL) cholesterol, are a well-known risk factor for heart disease, and variations in certain genes can affect these levels.

1. The APO Genes (APOA, APOB, APOC, APOE): Cholesterol Regulation
   The APO genes, which include APOA, APOB, APOC, and APOE, are involved in the regulation of lipoproteins, the particles that transport cholesterol and triglycerides in the bloodstream. These genes are pivotal in lipid metabolism, and mutations in them can lead to higher levels of “bad” cholesterol (LDL) and an increased risk of cardiovascular disease.³
   • APOE is perhaps the most well-studied of the APO genes, particularly the APOE4 allele. This variant is associated with higher levels of LDL cholesterol and an increased risk of  Alzheimer’s disease and atherosclerosis, both conditions in which the buildup of plaques restrict blood flow.¹ In contrast, the APOE2 variant is protective, lowering cholesterol levels and reducing the risk of these diseases.
   • APOB encodes a protein that is a key component of LDL cholesterol. Mutations in APOB are linked to familial hypercholesterolemia, a genetic disorder that results in extremely high LDL levels and early-onset heart disease. People with defective APOB proteins have difficulty clearing LDL from their bloodstream, leading to a buildup of cholesterol in the arteries.² The importance of this gene is also highlighted in various family-based studies of lipid disorders.⁴
   • APOC and APOA are also crucial in lipid regulation, with APOC1 linked to elevated triglycerides, while APOA is involved in raising levels of high-density lipoprotein (HDL) cholesterol, which helps remove cholesterol from the bloodstream. Lower levels of APOA have been associated with an increased risk of heart disease.²
2. LDLR Gene: The Cholesterol Receptor
   The LDLR gene encodes the LDL receptor, a protein that plays a critical role in removing LDL cholesterol from the bloodstream. Mutations in this gene are a primary cause of familial hypercholesterolemia (FH), a genetic condition in which individuals have abnormally high cholesterol levels from a young age. People with FH have a significantly increased risk of developing heart disease early in life. The LDLR gene mutation impairs the body’s ability to clear LDL cholesterol, leading to the buildup of plaque in arteries and an elevated risk of atherosclerosis.^1,4
3. PCSK9 Gene: Cholesterol Regulation at the Liver
   The PCSK9 gene is involved in regulating the number of LDL receptors in the liver. This gene plays a critical role in cholesterol homeostasis by controlling the degradation of LDL receptors. Mutations in PCSK9 can either increase or decrease cholesterol levels in the blood. Overactive PCSK9 results in fewer LDL receptors, leading to higher cholesterol levels and an increased risk of cardiovascular disease. On the other hand, some mutations lead to a loss-of-function effect, which increases the number of LDL receptors, lowers cholesterol levels, and reduces the risk of heart disease.² This discovery has been crucial for the development of PCSK9 inhibitors, a new class of drugs used to lower cholesterol levels and reduce the risk of heart disease.
4. CDKN2A and CDKN2B Genes: Cell Cycle Regulation and Atherosclerosis
   While cholesterol metabolism plays a central role in heart disease, other genes influence CVD risk by affecting the growth and behavior of cells in blood vessels. The CDKN2A and CDKN2B genes are involved in the regulation of the cell cycle—essentially how cells grow, divide, and maintain function. These genes help control the proliferation of vascular smooth muscle cells, which form part of the arterial walls.
   Mutations in CDKN2A and CDKN2B genes can lead to vascular smooth muscle cell dysfunction, which contributes to the formation of atherosclerotic plaques in the arteries. Over time, these plaques can narrow blood vessels, making it harder for blood to flow and increasing the risk of heart attacks and strokes.³ These findings underscore the importance of understanding genetic influences on vascular health, beyond just cholesterol regulation.⁴

Could Genetic Testing Change How We Prevent Heart Disease?

As our understanding of the genetics behind cardiovascular disease grows, so does the potential for personalized medicine. Genetic testing, like the MY DNA genome test by Alimentum Labs, can now identify individuals who carry genetic mutations linked to higher cholesterol or an increased risk of heart disease. This knowledge can help practitioners make more informed decisions about prevention and treatment.⁴

• Early Detection: Genetic tests can help identify people at higher risk for heart disease, even before symptoms appear. For example, genetic testing for LDLR mutations can potentially diagnose familial hypercholesterolemia early, allowing for early intervention to manage cholesterol levels and reduce the risk of heart disease.²
• Personalized Treatment: Genetic information can guide decisions about the best medications or treatments for individuals. For example, someone with a PCSK9 mutation might benefit from PCSK9 inhibitors, a medication specifically designed to lower cholesterol levels in patients with certain genetic variations.⁴
• Informed Lifestyle Choices: Understanding your genetic predispositions can motivate lifestyle changes, such as dietary modifications, specific exercise regimens, and nutritional supplement protocols tailored to your specific genetic risk factors.³
  

Genetic Insights into Cardiovascular Disease: The Future of Risk Prediction

The future of cardiovascular disease prevention lies in the integration of genetic data into personalized risk assessments. As researchers continue to identify additional genetic markers, we will be able to predict CVD risk with greater accuracy. The current landscape of genetic testing for heart disease is advancing, and in the near future, it is likely that genetic screenings will become routine for those with a family history of cardiovascular issues.^1,4

• Advancements in Treatment: New treatments, such as PCSK9 inhibitors, are already helping those with genetic mutations lower their cholesterol levels. As research progresses, more therapies that target genetic mutations will become available, further improving heart disease outcomes.²
• Better Prevention: The more we understand about how genetics influence heart disease, the better we can prevent it. Genetic testing may allow us to predict cardiovascular disease in individuals who otherwise may not show signs, allowing for early intervention and better management.⁴
  

The Bottom Line: Genes and Heart Disease

Genetics plays a crucial role in cardiovascular disease, with key genes affecting cholesterol metabolism, blood vessel health, and the likelihood of plaque buildup. While environmental factors are important, genetic factors cannot be ignored. Some of the most significant genetic markers include the APO, LDLR, PCSK9, and CDKN2A/B genes, all of which impact cholesterol levels, arterial health, and plaque buildup.^1,3

As we continue to decode the genetic factors that influence heart disease, a more personalized approach will allow for more targeted prevention and treatment. If you are interested in seeing what Cardiometabolic traits you may be genetically predisposed to, including Atherosclerosis, Hypercholesterolemia, and Cardiovascular Disease, the MY DNA Test Kit from Alimentum Labs can show you what genetic mutations you carry that may increase your risk of developing these conditions. 

Armed with this knowledge, individuals can make more informed decisions about their heart health and take proactive steps in their daily routine to potentially prevent the onset of cardiovascular disease or manage it more effectively. Understanding your genetic risk is not just about knowing your DNA—it’s about using that knowledge to live a healthier, longer life.⁴

References 

1. Kathiresan, S., & Srivastava, D. (2012). Genetics of human cardiovascular disease. Cell, 148(6), 1242–1257. https://doi.org/10.1016/j.cell.2012.03.001
2. Varghese T. P. (2024). Genetic Markers of Cardiovascular Disease. Current problems in cardiology, 49(7), 102588. https://doi.org/10.1016/j.cpcardiol.2024.102588
3. Veljkovic, N., Zaric, B., Djuric, I., Obradovic, M., Sudar-Milovanovic, E., Radak, D., & Isenovic, E. R. (2018). Genetic Markers for Coronary Artery Disease. Medicina (Kaunas, Lithuania), 54(3), 36. https://doi.org/10.3390/medicina54030036

Vrablik, M., Dlouha, D., Todorovova, V., Stefler, D., & Hubacek, J. A. (2021). Genetics of Cardiovascular Disease: How Far Are We from Personalized CVD Risk Prediction and Management?. International journal of molecular sciences, 22(8), 4182. https://doi.org/10.3390/ijms22084182