Familial Hypercholesterolemia Genetics and How They Work
June 30, 2017
Familial hypercholesterolemia is basically high cholesterol that’s inherited. Although some who suffer from familial hypercholesterolemia (FH) may not have a healthy diet, there are many others who have an excellent diet and exercise regimen and still suffer from high cholesterol because it’s an inherited disorder. So, what causes familial hypercholesterolemia? The simple answer is genetic mutations, but here are some more details about how these genetic mutations work.
LDLR Gene Mutation
The most common cause of FH is a mutation in the LDLR gene. The LDLR gene helps the body create a protein called low-density lipoprotein receptor. This receptor binds to low-density lipoproteins, which many people know as LDLs. The LDLs carry the cholesterol in the blood, so LDL receptors (LDLR) help regulate cholesterol levels by removing LDLs from the blood. However, in those with FH, the LDLR gene has mutated causing fewer LDLRs to be produced in the cells. Another mutation prevents the LDLRs from properly removing the LDLs. This is what causes a high level of cholesterol in the bloodstream.
Other Gene Mutations
There are other less common gene mutations that can cause FH. The APOB, LDLRAP1, AND PCSK9 genes all produce proteins that allow the LDL receptors to function properly in removing LDLs from the bloodstream. But when any of these genes mutate, the receptors don’t work properly, resulting in high cholesterol, regardless of diet or exercise habits.
FH is most often inherited when a genetic mutation is inherited from 1 parent. If FH is inherited from both parents, the consequences are much more severe. This is much rarer than inheriting it from 1 parent. When one parent has FH, the risk of children inheriting the disease is 50%. Genetic mutations are inherited because they’re present in the egg or sperm cell, so the genetically modified DNA is then passed on.
Once someone is diagnosed with FH, the overall goal is to reduce cholesterol levels to reduce the chance of heart attack or stroke. This is done by starting (or continuing) a healthy diet. Fat must be less than 30% of calorie intake. Certain medications are almost always required as well. Statin drugs are the most common and most effective at lowering cholesterol levels.