In a hurry? Here’s what you need to know:
- Cholesterol is a powerful molecule with many roles in the body
- The APOB gene helps transport cholesterol through the bloodstream
- Changes in the APOB gene can decrease the body’s ability clear cholesterol from the blood—leading to a disease called Familial Hypercholesterolemia
- DNA testing can help people find out if they’re likely to have this disease
- Preventative steps can be taken to potentially avoid a serious health complication
Cholesterol is a powerful molecule. It’s used by your body to build hormones like testosterone and estrogen. It helps give cells in our body structure. As vital as it is, it also has the power to contribute to heart disease. With such power, it’s important for our bodies to keep control over the amount of cholesterol we have and where its stored. To do this, it relies on multiple genes, including the apolipoprotein-B gene (APOB).
APOB is responsible for making a protein known by the same name (APOB). Like other apolipoproteins, APOB has the important task of helping our body transport cholesterol from one location to the next. Cholesterol is transferred in tiny packages (known as lipoproteins) alongside fats, water, and various proteins. Where the cholesterol goes in the body is determined by the types of fat and proteins that are packaged with it inside the lipoproteins. When it is in high-density lipoproteins (HDLs), the cholesterol is sent to the liver where the cholesterol can be broken down. But when it’s packaged in low-density lipoproteins (LDLs), it’s sent to places in the body where cholesterol is needed. LDLs are generally considered “bad cholesterol” because they are more likely to get stuck in the bloodstream and contribute to heart disease. It’s in these LDL packages where APOB comes into play.
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In order for cholesterol to be unloaded from its package, the LDL particle has to first connect with the receiving cell—not unlike a plane trying to coordinate its landing at an airport. APOB and other proteins in the LDL particle help connect it to the receiving cell and initiate offloading of the cholesterol. In doing so, APOB helps clear cholesterol from the bloodstream and protects our bodies from heart disease.
Genetics of FH
Genetic testing is the gold standard for identifying people with FH. Research has shown that most people with FH will have variants in one of three genes: LDLR (60-80%), APOB (1-5%), and PCSK9 (0-3%). Notably, the APOB protein interacts the LDLR protein (made from the LDLR gene) in order to remove LDLs from the blood1.
Changes in the DNA coding for the APOB protein have been linked to a disease known as Familial Hypercholesterolemia (FH). FH is the most common form of inherited heart disease, affecting about one out of every 250-500 people1-3. Research has shown that changes in the DNA affecting cholesterol metabolism—including variants in APOB—result in chronically high blood levels of LDL cholesterol1-3. Because the cholesterol cannot be offloaded in its normal destination, the amount of LDLs in the blood rises. Some of that excess cholesterol can be mistakenly offloaded into the walls of blood vessels. Over time, this can cause inflammation and thickening of the blood vessels which can ultimately result in heart attacks and other symptoms of heart disease1,4.
Fortunately, there are ways to prevent serious health complications from FH. DNA testing—including the type of test offered for free as a part of the WholeMe project—can help identify people with variants associated with the condition. Once diagnosed, FH is typically treated with drugs called statins which help to lower blood cholesterol levels and can have a significant impact on reducing heart attack risk.
- Youngblom, Emily. “Familial Hypercholesterolemia.” Advances in Pediatrics., U.S. National Library of Medicine, 8 Dec. 2016, www.ncbi.nlm.nih.gov/books/NBK174884/.
- Bouhairie, Victoria Enchia, and Anne Carol Goldberg. “Familial Hypercholesterolemia.” Cardiology clinics 33.2 (2015): 169–179. PMC. Web. 22 Aug. 2018.
- Varghese, Mithun J. “Familial Hypercholesterolemia: A Review.” Annals of Pediatric Cardiology 7.2 (2014): 107–117. PMC. Web. 22 Aug. 2018.
- Wolinsky, H., et al. “Arterial Lysosomes and Connective Tissue in Primate Atherosclerosis and Hypertension.” Circulation Research, vol. 36, no. 4, Jan. 1975, pp. 553–561., doi:10.1161/01.res.36.4.553.