Familial Hypercholesterolemia, or FH, is a common inherited condition. It leads to high levels of LDL cholesterol from a young age. There are two forms, with the homozygous type less common than the heterozygous.
DNA changes, called mutations, in genes like Apolipoprotein B (ApoB) lead to FH. Most cases are due to mutations in the LDLR gene. To diagnose FH, doctors check your cholesterol levels.
Lifestyle changes and medication like statins are common treatment methods for FH. But, new treatments like gene therapy and stem cell therapy are being researched. These approaches show promise for the future of managing FH.
Key Takeaways:
- Familial hypercholesterolemia (FH) is an inherited genetic cholesterol disorder characterized by high cholesterol levels.
- FH can manifest as homozygous (HoFH) or heterozygous FH (HeFH) forms, with HeFH being more prevalent.
- Mutations in genes such as LDLR, ApoB, and PCSK9 contribute to FH development.
- Diagnosis of FH involves screening non-HDL cholesterol or LDL cholesterol levels.
- Treatment options for FH include lifestyle changes, statins, and nonstatin therapy.
Epidemiology and Prevalence of Familial Hypercholesterolemia
Familial hypercholesterolemia (FH) is a genetic disorder known for high levels of bad cholesterol from birth. Knowing the numbers and types of people with FH helps in treating and preventing it.
Worldwide, about 20 million people have FH, but sadly, most don’t know it. FH shows up more in some places, like Asia, where about 0.19% have it. In Europe and North America, the rate is around 0.32%. This can be due to differences in our genes and where we live.
Heterozygous FH Prevalence
Heterozygous FH (HeFH) is the common type, found in about 1 out of 200 to 250 people. Catching HeFH early can help slow down the disease and lower the chance of heart problems.
Homozygous FH Prevalence
Homozygous FH (HoFH) is less common but more serious. It affects around 1 in every 100,000 to 160,000 people. HoFH makes even higher bad cholesterol levels, raising the risk of heart disease early in life. Spotting HoFH soon and acting fast are crucial for better health outcomes.
People are working hard to spread the word about FH and make it easier to find and treat. Identifying and helping those with FH aims to lessen heart diseases’ impact.
Causes and Pathogenesis of Familial Hypercholesterolemia
Familial hypercholesterolemia (FH) comes from changes in genes that handle cholesterol. The main changes happen in the LDLR gene. This gene affects the low-density lipoprotein receptor. Changes in the APOB and PCSK9 genes can also bring about FH.
Changes in the LDLR gene are the biggest reason for FH. They stop the body from making the right LDL receptor or binding it correctly. This makes LDL cholesterol (LDL-C) levels too high. And high LDL-C is a key sign of FH. It adds to problems like heart disease.
Changes in the APOB gene can also cause FH. This gene makes the apolipoprotein B protein for LDL particles. If the protein can’t attach to the LDL receptor because of changes, LDL-C stays high. This increases the chance of heart issues.
PCSK9 is another gene linked to FH. Changes in this gene can make the LDL receptor less effective, causing LDL-C to stay high. This makes FH more likely. Some changes in PCSK9 may also help remove the LDL receptor faster. This also makes FH worse.
Even though most FH cases come from LDLR, APOB, and PCSK9, a few others genes can sometimes add to the problem. FH can even be from many genes at once, leading to really high LDL-C.
Genes associated with Familial Hypercholesterolemia
| Gene | Function | Role in FH |
|---|---|---|
| LDLR | Encodes the LDL receptor protein | Impaired synthesis or binding leads to elevated LDL-C levels |
| APOB | Encodes apolipoprotein B, a component of LDL particles | Mutations prevent binding to the LDL receptor, causing LDL-C accumulation |
| PCSK9 | Regulates LDL receptor degradation | Mutations can lead to reduced LDL receptor expression or increased degradation |
Knowing the root causes of FH is key to managing and diagnosing the disease. Pinpointing these gene changes helps in making treatments just for the person. This way, we can lower LDL-C and the risk of heart problems.
Stem Cell Therapy and the Future of Familial Hypercholesterolemia Treatment
Stem cell therapy, using induced pluripotent stem cells (iPSCs), shows hope in treating familial hypercholesterolemia (FH). This is a genetic cholesterol issue marked by high LDL-C. iPSCs are like blank cells that can turn into liver cells and potentially correct the flawed gene in FH.
Gene therapy is another approach for FH. Scientists aim to permanently fix the broken LDLR gene with this method. But, this method’s success needs the new gene to work long-term, get into liver cells well, and function effectively [28].
Progress in gene and cell therapies might transform how we handle FH. It could result in better lowering of bad cholesterol and outcomes for patients. There’s a lot of hope for these new treatments and their potential to help those with FH [29, 28].