Hypercholesterolemia and genetics
Hypercholesterolemia is a condition characterized by elevated levels of cholesterol in the bloodstream, which can lead to serious health issues such as cardiovascular disease and atherosclerosis. Cholesterol is a vital lipid necessary for many bodily functions, but excessive amounts can accumulate in the arteries, posing significant health risks. Genetics plays a crucial role in hypercholesterolemia, particularly in familial cases where it is inherited in an autosomal dominant manner. Individuals with familial hypercholesterolemia often experience high LDL ("bad") cholesterol levels due to defects in the LDL receptor, which impairs the body’s ability to clear LDL from the blood.
Environmental factors, such as diet and lifestyle, also contribute to cholesterol levels; thus, individuals with a family history of heart disease are encouraged to adopt healthier habits. Certain ethnic groups may exhibit varying cholesterol levels, with those from northern Europe generally having higher levels than those from southern Europe or Asian descent. Although hypercholesterolemia may often be asymptomatic, it can lead to severe complications, including heart attacks and strokes. Regular screening is recommended to monitor cholesterol levels, allowing for early intervention through dietary changes or medications like statins if necessary. Overall, a combination of genetic predisposition and lifestyle choices is pivotal in managing cholesterol levels effectively.
Hypercholesterolemia and genetics
DEFINITION Hypercholesterolemia occurs when the body is unable to use or eliminate excessive amounts of cholesterol. Cholesterol is a steroid lipid, a type of fat molecule that is essential for life. It is an important component of cell membranes and is used by the body to synthesize various steroid hormones. When cooled, cholesterol is a waxy substance, which cannot dissolve in the bloodstream. It is transported in the bloodstream in complexes of cholesterol and protein called lipoproteins.
There are two different classes of lipoproteins in the bloodstream. Low-density lipoprotein (LDL) cholesterol is the “bad” cholesterol that tends to deposit into the tissues, especially in the vessel walls. High-density lipoprotein (HDL), a smaller, denser molecule, is the “good” cholesterol, because it can transport cholesterol from tissues to the liver. About one tablespoon of cholesterol circulates in the bloodstream, which is enough to meet the body’s needs. Cholesterol naturally exists in animal products, such as meats (particularly fatty meats), eggs, milk, cheese, liver, and egg yolks. Large intakes of these products can certainly increase one’s cholesterol level, not only because they have high concentrations of cholesterol itself but, more important, because they contain fats that prompt the body to make cholesterol. Cholesterol is also produced by the liver. The liver manufactures and regulates the amount of lipoproteins in the body. The normal range of total cholesterol is less than 200 milligrams per deciliter (mg/dl) of blood. A total cholesterol level between 200-240 mg/dl is borderline high, and a total cholesterol level above 240 mg/dl is considered high. The normal range of LDL cholesterol is less than 130 mg/dl, and the normal range of HDL cholesterol is greater than 35 mg/dl. Hypercholesterolemia is diagnosed when the total cholesterol level is higher than the normal range, and the term “hypercholesterolemia” is often used to refer to familial cholesterolemia as well.
Risk Factors
Individuals who smoke, are obese, eat foods that are high in cholesterol (such as red meat and full-fat dairy products), do not exercise, have high blood pressure, or have diabetes are at risk for hypercholesterolemia. If an individual has high cholesterol levels and a parent or sibling who developed heart disease before the age of fifty-five, the individual will have an increased risk of also developing heart disease.
It is evident that hypercholesterolemia is more common among certain ethnic groups. Cholesterol levels in people from northern European countries are higher than in those from southern Europe. Asians have lower cholesterol levels than Caucasians. A severe form of hereditary hypercholesterolemia called familial hypercholesterolemia typically does not respond to lifestyle changes.
Etiology and Genetics
There is no doubt that genes play an important role in the occurrence of hypercholesterolemia. Familial hypercholesterolemia is the best understood genetically. It displays autosomal dominant inheritance, which means that either parent with hypercholesterolemia has a high probability of passing it on. This disorder results from defects of the LDL receptor, which ensures the proper movement of LDLs. Thus, dysfunction of this receptor causes increased levels of LDL in the blood. The LDL receptor gene, which is located on the short arm of human chromosome 19, is prone to a variety of mutations that affect LDL metabolism and movement.
Apolipoprotein B (Apo-B) is a protein essential for cholesterol transport. can be affected by both diet and genetics. Individuals with one or more specific genotypes (the genetic constitution of an individual) have much greater changes in cholesterol levels in response to diet than do other genotypes.
The other genetic cause is mutations in the gene for the enzyme cholesterol 7-alpha hydroxylase (CYP7A1), which is essential for the normal elimination of cholesterol in the blood. It initiates the primary conversion of cholesterol into bile acids in the liver. Mutations can cause an accumulation of cholesterol in the liver, as the primary route of converting cholesterol to bile acids is blocked. The liver responds to excessive cholesterol by reducing the number of receptors available to take up LDL from the blood, resulting in an accumulation of LDL in the blood.
Symptoms
Hypercholesterolemia itself may be asymptomatic but can still be damaging to the vascular system. Excess amounts of cholesterol in the blood can build up along the walls of the arteries, which results in hardening and narrowing of the arteries, called atherosclerosis. Severe atherosclerosis can lead to a blockage of blood flow. Atherosclerosis in the heart causes cardiovascular disease (such as heart attacks). The result of atherosclerosis in the brain can be a stroke. Atherosclerosis can also occur in the extremities of the body, such as the legs, causing pain and blood clots.
Several diseases can contribute to hypercholesterolemia, such as diabetes, thyroid disorders, and liver diseases. However, the most important cause of hypercholesterolemia is a combination of diet and genetic factors.
Hypercholesterolemia is on the increase worldwide. People with hypercholesterolemia often develop coronary heart disease at a younger age than those in a general population as a result of increased LDL cholesterol levels (about two times higher than normal). In cases of extreme hypercholesterolemia (exceeding three or four times normal), high cholesterol levels can be detected in utero or at birth in cord blood. Individuals with extreme hypercholesterolemia usually develop the first cardiovascular event in childhood or adolescence and die by the age of thirty.
Screening and Diagnosis
A blood test called a lipid panel or lipid profile can check cholesterol levels. The test typically reports an individual’s total cholesterol, LDL and HDL cholesterol, and triglycerides—a type of fat in the blood.
Treatment and Therapy
Although genetics plays an important role, hypercholesterolemia is often the result of a combination of genetics and lifestyle. Consuming a healthy diet and exercising regularly can help maintain an optimal cholesterol level and reduce the risk of cardiovascular disease for people with either a good gene or a bad gene.
If lifestyle changes fail to lower cholesterol levels, the doctor may recommend medication. Statins, such as atorvastatin (Lipitor), fluvastatin (Lescol), lovastatin (Altoprev, Mevacor), pravastatin (Pravachol), rosuvastatin (Crestor) and simvastatin (Zocor), are a commonly prescribed treatment. These drugs deplete cholesterol in liver cells, causing the liver to remove cholesterol from the blood. Bile-acid-binding resins, including cholestyramine (Prevalite, Questran), colesevelam (Welchol), and colestipol (Colestid), bind to bile acids in the liver. This causes the liver to use its excess cholesterol to produce more bile acids, reducing the levels of cholesterol in the blood.
Another class of drugs, like the drug ezetimibe (Zetia), are cholesterol absorption inhibitors. These drugs decrease the amount of dietary cholesterol that is absorbed in the small intestine and released into the bloodstream. Zetia can be used with any of the statin drugs. Similarly, the combination drug ezetimibe-simvastatin (Vytorin) decreases both the dietary cholesterol absorbed in the small intestine and the cholesterol produced in the liver. A doctor may also prescribe medication to decrease high levels of triglycerides.
Prevention and Outcomes
Individuals can control their cholesterol levels by eating low-fat diets, maintaining healthy body weights, exercising regularly, and not smoking. They should also receive cholesterol and triglyceride screening to identify and treat abnormal levels. This screening is recommended for men between the ages of twenty and thirty-five and women between the ages of twenty and forty-five.
Bibliography
Abrams, Jonathan, ed. Cholesterol Lowering: A Practical Guide to Therapy. London: Arnold, 2003. Print.
Cohen, Jay S. What You Must Know About Statin Drugs and Their Natural Alternatives: A Consumer’s Guide to Safely Using Lipitor, Zocor, Mevacor, Crestor, Pravachol, or Natural Alternatives. Garden City Park: Square One, 2005. Print.
Eckel, Robert H. Metabolic Risk for Cardiovascular Disease. Dallas: Amer. Heart Assn., 2010. Print.
Freeman, Mason W., and Christine Junge. The Harvard Medical School Guide to Lowering Your Cholesterol. New York: McGraw, 2005. Print.
Goldstein, J. L., H. H. Hobbs, and M. S. Brown. “Familial Hypercholesterolemia.” The Metabolic and Molecular Bases of Inherited Disease. Ed. C. R. Scriver et al. 7th ed. New York: McGraw, 1995. Print.
Gunder, Laura M., and Scott A. Martin. Essentials of Medical Genetics for Health Professionals. Sudbury: Jones, 2011. Print.
Rantala, M., et al. “Apolipoprotien B Gene Polymorphisms and Serum Lipids: Meta-Analysis and the Role of Genetic Variation in Responsiveness to Diet.” American Journal of Clinical Nutrition 71.3 (2000): 713–24. Print.
Sauer, Heinrich, Ajay M. Shah, and Francisco R. M. Laurindo. Studies on Cardiovascular Disorders. New York: Humana, 2010. Print.
Steinberg, Daniel. The Cholesterol Wars: The Skeptics Versus the Preponderance of Evidence. San Diego: Academic, 2007. Print.
Vrablik, Michal. "Genetics of Familial Hypercholesterolemia: New Insights." Frontiers in Genetics, 7 Oct. 2020, doi.org/10.3389/fgene.2020.574474. Accessed 4 Sept. 2024.
"What Is Familial Hypercholesterolemia? American Heart Association, 19 Feb. 2024, www.heart.org/en/health-topics/cholesterol/genetic-conditions/familial-hypercholesterolemia-fh. Accessed 4 Sept. 2024.