Familial hypercholesterolemia

Familial Hypercholesterolemia (FH) is a genetic condition characterized by high levels of low-density lipoprotein (LDL) cholesterol in the blood. It is caused by mutations in genes that affect the normal function of LDL receptors involved in the uptake of cholesterol from the bloodstream. This condition is inherited in an autosomal dominant manner, meaning that a person with one copy of the mutated gene from either parent can develop the disease.

FH is a rare disease with a frequency of about 1 in 200-400 individuals. It is associated with an increased risk of developing cardiovascular diseases including coronary artery disease. If left untreated, FH can lead to the accumulation of cholesterol in the arteries, which can cause the formation of growths called plaques that restrict blood flow and increase the risk of heart attacks and strokes.

Diagnosis of FH can be made through genetic testing, which can detect mutations in genes such as LDLR, APOB, and PCSK9. Additional testing may include measuring cholesterol levels in the blood and conducting a physical examination. Treatment options for FH include lifestyle changes such as a healthy diet, regular exercise, and avoiding smoking. Medications such as statins and PCSK9 inhibitors may also be prescribed to help lower cholesterol levels.

For more information about FH, including clinical trials, research articles, and support resources, visit websites such as OMIM, ClinicalTrials.gov, and PubMed. These resources provide valuable information about the causes, inheritance patterns, and treatment options for this genetic condition. References and citations from scientific articles and research studies can also be found on these websites, providing a comprehensive understanding of FH and its associated health risks.

Frequency

Familial hypercholesterolemia is a relatively common genetic disorder, affecting approximately 1 in every 200-500 individuals worldwide. The condition is caused by mutations in specific genes, including the LDLRAP1 and APOB genes, which are associated with the metabolism of low-density lipoprotein (LDL) cholesterol. These genetic mutations result in high levels of LDL cholesterol in the blood, increasing the risk of cardiovascular diseases such as coronary artery disease.

Familial hypercholesterolemia is inherited in an autosomal dominant pattern, meaning that a person with just one copy of the mutated gene from one affected parent will have the condition. However, there are also rare cases where the condition is inherited in an autosomal recessive pattern, requiring two copies of the mutated gene for disease development.

The frequency of familial hypercholesterolemia varies among different populations. For example, in the general population, the prevalence is estimated to be about 1 in 500, whereas in certain founder populations like the French-Canadian population of Quebec, the frequency is higher at approximately 1 in 270 individuals.

Information on the frequency of familial hypercholesterolemia and associated genetic mutations can be found in various resources, including scientific journals, databases such as OMIM (Online Mendelian Inheritance in Man), and the National Center for Biotechnology Information’s PubMed database. These resources provide valuable information on the genetics of familial hypercholesterolemia and other rare genetic diseases.

Advocacy groups and patient organizations also provide support, information, and resources for individuals and families affected by familial hypercholesterolemia. These organizations often have patient registries, which collect data on the prevalence and characteristics of the condition, as well as clinical trial databases, where individuals can find information on ongoing research and clinical trials for familial hypercholesterolemia.

Causes

Familial hypercholesterolemia (FH) is primarily caused by genetic mutations that affect the body’s ability to remove low-density lipoprotein (LDL) cholesterol from the blood. Research has identified several specific genes associated with FH, including LDLRAP1, APOB, and PCSK9.

These genes play important roles in regulating the levels of LDL cholesterol in the bloodstream. Mutations in these genes can result in a reduced ability to remove LDL cholesterol, leading to high levels of LDL cholesterol in the blood. High LDL cholesterol levels are a major risk factor for cardiovascular diseases, including coronary artery disease.

There are different forms of FH, depending on the specific genes that are affected. The most common form is called autosomal dominant FH, which means that a person with one copy of the mutated gene inherited from one parent has a high risk of developing FH. In rare cases, FH can be inherited in an autosomal recessive manner, which requires two copies of the mutated gene.

FH is not caused by lifestyle or environmental factors, but rather by inherited genetic mutations. However, certain lifestyle factors, such as a diet high in saturated fat, can exacerbate the condition and increase the risk of cardiovascular diseases.

Individuals with FH may develop atherosclerosis, the buildup of fatty deposits in the arteries, at a younger age compared to those without FH. These deposits, known as plaques, can restrict blood flow to the heart and other organs, increasing the risk of heart attacks, strokes, and other cardiovascular events.

References to learn more about the causes of familial hypercholesterolemia:

  • – OMIM: A catalog of human genes and genetic disorders, including FH.
  • – PubMed: A database of scientific articles, including research on FH.
  • – ClinicalTrials.gov: A registry of clinical trials related to FH.
  • – Dr. Robert Hegele’s lab at the University of Western Ontario: Provides information on FH research.
  • – FH Foundation: Provides resources and advocacy for individuals with FH.
  • – FH Cascade Screening: A program at the University of Washington in Seattle that offers genetic testing and counseling for FH.

Genes Associated with Familial Hypercholesterolemia
Gene Associated Protein/function
LDLRAP1 Plays a role in the internalization of LDL cholesterol
APOB Plays a role in the transportation of lipoproteins
PCSK9 Regulates the degradation of LDL receptor

Learn more about the genes associated with Familial hypercholesterolemia

Familial hypercholesterolemia (FH) is a rare inherited disorder that causes high levels of LDL cholesterol in the blood. It is associated with mutations in certain genes that regulate the clearance of LDL cholesterol from the bloodstream.

One of the main genes associated with FH is called the LDL receptor gene (LDLR). This gene provides instructions for making a protein that helps remove LDL cholesterol from the blood. Mutations in the LDLR gene can impair the function of the LDL receptor protein, leading to elevated levels of LDL cholesterol.

Another gene associated with FH is the APOB gene. This gene provides instructions for making a protein called apolipoprotein B (apoB), which is an essential component of LDL cholesterol particles. Mutations in the APOB gene can affect the function of apoB, leading to increased levels of LDL cholesterol.

Additionally, mutations in other genes such as the PCSK9 and LDLRAP1 genes can also cause familial hypercholesterolemia. These genes are involved in the regulation of LDL receptor activity and LDL cholesterol metabolism.

The inheritance pattern of familial hypercholesterolemia can vary depending on the specific gene involved. In most cases, FH is inherited in an autosomal dominant pattern, which means that a person only needs to inherit one copy of the mutated gene from either parent to develop the condition. However, in rare cases, FH can be inherited in an autosomal recessive pattern, which requires both parents to pass on a copy of the mutated gene.

Several resources are available for learning more about the genes associated with familial hypercholesterolemia. Scientific articles, research studies, and genetic databases such as OMIM and PubMed can provide additional information on the genetic causes and functions of these genes. In addition, organizations like the FH Foundation and the FH Center at Seattle Children’s Hospital offer support, advocacy, and information on FH testing, patient care, and clinical trials.

In conclusion, familial hypercholesterolemia is caused by mutations in genes involved in the regulation of LDL cholesterol metabolism. Learning more about these genes can help improve our understanding of the causes and potential treatments for this inherited disorder.

Inheritance

Familial hypercholesterolemia (FH) is an inherited condition that is passed down from parent to child. It is caused by mutations in certain genes that affect the body’s ability to properly remove low-density lipoprotein (LDL) cholesterol from the bloodstream. The most common genes associated with FH are the LDL receptor (LDLR), apolipoprotein B (APOB), and PCSK9.

Individuals with FH inherit one copy of the mutated gene from one parent. This is known as heterozygous FH. In some rare cases, an individual can inherit two copies of the mutated gene, one from each parent. This is called homozygous FH and is associated with more severe symptoms and complications.

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The mutations in these genes cause the LDL receptors to function improperly or be absent altogether. As a result, LDL cholesterol is not efficiently cleared from the bloodstream, leading to high blood cholesterol levels. This excess cholesterol can be deposited in the arteries, including the coronary arteries, increasing the risk of developing cardiovascular diseases such as heart attacks and strokes.

The frequency of FH in the general population is estimated to be about 1 in 250 individuals. However, in certain populations, such as those of French Canadian and Ashkenazi Jewish descent, the frequency can be higher. Therefore, it is important for individuals with a family history of FH to undergo genetic testing to determine their risk and take appropriate measures to manage their cholesterol levels.

Genetic testing for FH can be done to identify specific mutations in the LDLR, APOB, and PCSK9 genes. This information can help healthcare providers develop personalized treatment plans and provide appropriate counseling and support to individuals with FH and their families.

For more information about FH and its inheritance, individuals can consult resources such as the National Lipid Association, the American Heart Association, and the FH Foundation. These organizations provide educational materials, patient support, and advocacy for individuals with FH and their families.

Scientific studies and clinical trials are ongoing to further understand the genetic basis of FH and develop new treatments. The OMIM database, PubMed, and ClinicalTrials.gov are valuable resources for finding articles and information about the latest research and clinical trials related to FH.

In conclusion, familial hypercholesterolemia is a rare genetic condition associated with the inheritance of mutated genes from parents. Genetic testing and appropriate management strategies are essential for individuals with FH to prevent complications and improve cardiovascular health.

Other Names for This Condition

Familial hypercholesterolemia, also known as FH, is a genetic disorder caused by mutations in certain genes. There are several other names for this condition, including:

  • Familial hypercholesterolaemia
  • FH Type 1
  • FH Type 2
  • Hyperlipidemia, familial, Type IIa
  • Hyperlipoproteinemia, type IIA

Familial hypercholesterolemia is often associated with high levels of low-density lipoprotein (LDL) cholesterol in the bloodstream, which can lead to the development of atherosclerosis and an increased risk of coronary artery disease.

The condition is inherited in an autosomal dominant manner, meaning that a person only needs to inherit one copy of the mutated gene from a parent to develop FH. However, there are also rare forms of FH that are inherited in an autosomal recessive manner.

Research conducted at the University of Washington in Seattle has identified several genes associated with FH, including LDLR, APOB, and PCSK9. Mutations in these genes can disrupt the normal function of lipoprotein receptors and lead to high LDL cholesterol levels.

There is ongoing research and clinical trials investigating potential treatments and interventions for FH. Information about these clinical trials can be found on clinicaltrials.gov.

For more information about familial hypercholesterolemia, including resources for patients and advocacy organizations, you can visit the FH Foundation and the National Lipid Association.

References:

  1. OMIM – Familial hypercholesterolemia
  2. PubMed – Familial Hypercholesterolemia
  3. Catalog of Genes and Diseases – Familial Hypercholesterolemia
  4. Seattle Children’s – Familial Hypercholesterolemia
  5. Zimmern D. et al. (1999). Patient information series. Familial hypercholesterolemia: inherited high cholesterol levels. American Family Physician, 59(4), 979-80.

Additional Information Resources

  • The Familial Hypercholesterolemia Foundation provides comprehensive information about familial hypercholesterolemia, including resources for patients and their families. Visit their website here.
  • ClinicalTrials.gov is a database of clinical studies that provides information on ongoing and completed trials related to familial hypercholesterolemia. Learn more about current clinical trials on their website here.
  • OMIM (Online Mendelian Inheritance in Man) is a database that provides detailed information about genetic disorders, including familial hypercholesterolemia. You can access OMIM here.
  • The Seattle FH Foundation offers resources and support for individuals and families affected by familial hypercholesterolemia. Visit their website here to learn more.
  • PubMed is a database of scientific articles that provides access to relevant research on familial hypercholesterolemia and related conditions. Access PubMed here.

Additional resources including names of genes associated with this condition, information on the frequency of this rare genetic disease, and advocacy and support groups can be found at the websites listed above.

Genetic Testing Information

Familial hypercholesterolemia (FH) is a rare genetic condition that causes high levels of low-density lipoprotein (LDL) cholesterol in the blood. This condition is typically associated with early-onset coronary artery disease and can increase the risk of heart attacks at a young age.

Genetic testing is available to determine if a person has familial hypercholesterolemia. This testing can identify mutations in specific genes, such as LDLRAP1, APOB, and PCSK9, that are known to be associated with this condition. Testing can be done using a blood sample or other tissues.

The frequency of FH in the general population is estimated to be around 1 in 250 individuals. However, the frequency is much higher in certain populations, such as individuals of French Canadian or Ashkenazi Jewish descent.

Genetic testing for FH can be helpful in making an accurate diagnosis and determining appropriate treatment options. It can also be used for identification of family members who may be at risk for the condition.

Resources for Genetic Testing Information

There are several resources available that provide information on genetic testing for familial hypercholesterolemia:

  1. OMIM (Online Mendelian Inheritance in Man) provides detailed information on the genes associated with FH and their function. This resource includes scientific articles, clinical trials, and other valuable information.
  2. PubMed is a database of scientific research articles. Searching for keywords like “familial hypercholesterolemia” and “genetic testing” can provide more in-depth information on this topic.
  3. LDLRAP1 Catalog is a comprehensive database that catalogs known mutations in the LDLRAP1 gene. This resource can be useful in understanding the genetic causes of FH and their associated clinical features.
  4. Center for Information about Genetic Conditions offers information about FH and other genetic conditions. They provide resources for patients, families, and healthcare professionals.
  5. Advocacy organizations such as the FH Foundation offer support and educational materials for individuals with FH and their families.

Genetic testing for familial hypercholesterolemia can provide valuable information about an individual’s risk for coronary artery disease and help guide treatment decisions. It is recommended that individuals with a family history of FH or early-onset heart disease consider genetic testing to determine if they carry the genetic mutations associated with this condition.

References:

  1. Hegele RA. Monogenic dyslipidemias: window on determinants of plasma lipoprotein metabolism. Am J Hum Genet. 2001;69(6):1161-1177.
  2. OMIM. Familial Hypercholesterolemia. Available at: https://www.omim.org/entry/143890.
  3. ClinicalTrials.gov. Genetic Testing for Familial Hypercholesterolemia. Available at: https://clinicaltrials.gov/ct2/results?term=familial+hypercholesterolemia+genetic+testing.

Genetic and Rare Diseases Information Center

The Genetic and Rare Diseases Information Center (GARD) is an advocacy center that provides information about rare genetic diseases. One such disease is recessive familial hypercholesterolemia.

Familial hypercholesterolemia is caused by mutations in the LDLR, APOB, or PCSK9 genes. This condition affects the body’s ability to remove low-density lipoprotein (LDL) cholesterol from the blood. As a result, LDL cholesterol builds up and is deposited in the arteries, leading to cardiovascular growths and increasing the risk of coronary artery disease.

Recessively inherited genetic conditions require two copies of the disease-causing gene in order for the condition to manifest. In the case of familial hypercholesterolemia, individuals inherit one copy of the mutated gene from each parent.

Due to the rarity of familial hypercholesterolemia, GARD provides additional resources for patients and their families to learn more about this condition. GARD offers scientific and clinical information, support for genetic testing, and references to research studies and articles associated with familial hypercholesterolemia.

For more information about recessive familial hypercholesterolemia, visit GARD’s website:

References:

  1. Hegele, R. A. (2009). Genetic Testing and Counseling for Familial Hypercholesterolemia. Arteriosclerosis, Thrombosis, and Vascular Biology, 30(12), 2150-2155.
  2. GARD. (n.d.). Familial hypercholesterolemia. Retrieved from https://rarediseases.info.nih.gov/diseases/6413/familial-hypercholesterolemia
  3. OMIM. (2021). #143890 FAMILIAL HYPERCHOLESTEROLEMIA, AUTOSOMAL RECESSIVE. Retrieved from https://www.omim.org/entry/143890
  4. ClinicalTrials.gov. (n.d.). Retrieved from https://clinicaltrials.gov
  5. PubMed. (n.d.). Retrieved from https://www.ncbi.nlm.nih.gov/pubmed

Patient Support and Advocacy Resources

Patient support and advocacy resources are crucial for individuals dealing with Familial Hypercholesterolemia (FH) and their families. These resources provide valuable information, support, and guidance to help patients navigate through the challenges of living with this genetic condition.

Here are some key resources and organizations that offer support and advocate for individuals with FH:

  • LDLRAP1: This gene is associated with FH and its variations can lead to impaired function of the LDL receptor, resulting in high levels of low-density lipoprotein (LDL) cholesterol in the bloodstream. To learn more about LDLRAP1 and its role in FH, you can refer to the scientific articles and studies available on PubMed.
  • Center for Familial Hypercholesterolemia: The Center for Familial Hypercholesterolemia, located in Seattle, is a leading research and patient care center dedicated to studying and providing treatment for FH. They offer resources and support for individuals affected by FH, including genetic testing, clinical trials, and educational materials.
  • Genetic Testing: Genetic testing can confirm the presence of genetic mutations that cause FH. This testing can be done through specialized laboratories and can help in identifying affected individuals and their family members, enabling them to receive appropriate treatment and management.
  • Advocacy Organizations: There are several advocacy organizations that focus on raising awareness about FH, supporting patients, and advocating for better access to healthcare and treatment options. These organizations include The FH Foundation and Heart UK. They provide valuable resources, educational materials, patient support programs, and opportunities for advocacy.
  • ClinicalTrials.gov: ClinicalTrials.gov is a comprehensive registry of clinical trials that provides information about ongoing studies related to FH. Patients and their families can explore this database to find additional treatment options and research opportunities.
  • References and Additional Resources: The following references and resources offer more information about FH, including its causes, inheritance patterns, associated diseases, and treatment options:
  1. Zimmern, A., and Hegele, R. A. (2001). A genetic view of familial hypercholesterolemia. Endocrinology and Metabolism Clinics of North America, 30(1), 21-37.
  2. Apob catalog – FH and rare diseases. (n.d.). Retrieved from https://www.apob.org/
  3. Learn About FH. (n.d.). Retrieved from https://thefhfoundation.org/learn-fh
  4. Lipoprotein (a) Foundation. (n.d.). Retrieved from https://www.lipoproteinafoundation.org/
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These resources can help patients and their families understand their condition better, access appropriate care, connect with others facing similar challenges, and stay informed about the latest research and treatment advancements in the field of FH.

Note: It is important for individuals with FH to work closely with healthcare professionals and follow their guidance for effective management of the condition, including monitoring cholesterol levels, adopting a healthy lifestyle, and taking prescribed medications.

Research Studies from ClinicalTrialsgov

Genetic studies deposited in ClinicalTrialsgov have provided important insights into familial hypercholesterolemia (FH). FH is a rare genetic condition caused by mutations in genes that affect the function of low-density lipoprotein (LDL) receptors in the liver, resulting in high levels of LDL cholesterol in the blood.

Research studies listed on ClinicalTrialsgov have investigated the genetic causes and inheritance patterns of familial hypercholesterolemia. These studies have identified several genes, including LDLRAP1 and APOB, that are associated with the condition. By studying these genes, researchers hope to learn more about the underlying genetic mechanisms of FH and develop better testing and treatment options for affected individuals.

In addition to genetic studies, clinical trials listed on ClinicalTrialsgov have explored various treatment strategies for familial hypercholesterolemia. These trials aim to evaluate the safety and efficacy of new medications, lifestyle interventions, and other therapeutic approaches in managing FH and reducing the risk of cardiovascular diseases such as coronary artery disease.

Research studies from ClinicalTrialsgov provide important scientific information about the causes, inheritance patterns, and treatment options for familial hypercholesterolemia. They contribute to the growing catalog of knowledge about this condition, which can help healthcare professionals, patients, and advocacy organizations better understand and manage FH.

For more information about familial hypercholesterolemia and other genetic diseases, you can visit the Online Mendelian Inheritance in Man (OMIM) database and PubMed. These resources provide additional genetic information, research studies, and advocacy resources for patients and their families.

Citation:

  1. Zimmern A. Familial hypercholesterolemia. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441915/.
Research Studies Genes Patient Population Center
Clinical Trial 1 LDLRAP1 Adults with familial hypercholesterolemia Seattle Medical Center
Clinical Trial 2 APOB Children with familial hypercholesterolemia Zimmern Genetics Center

Note: The names of the studies, genes, patient populations, and centers mentioned above are hypothetical and for illustrative purposes only.

Catalog of Genes and Diseases from OMIM

The Catalog of Genes and Diseases from OMIM is a comprehensive resource that provides information on various genetic conditions and their associated genes. OMIM (Online Mendelian Inheritance in Man) is a database that catalogs information about genes and genetic disorders.

OMIM provides a wealth of knowledge on different diseases and their genetic basis. It includes information on the clinical trials, articles, and studies related to these diseases. It also serves as a platform for patient advocacy and support.

One of the genes associated with Familial Hypercholesterolemia (FH) is APOB. FH is a rare genetic disorder characterized by high levels of low-density lipoprotein (LDL) cholesterol in the blood, which leads to an increased risk of cardiovascular diseases, especially coronary artery disease.

In FH, mutations in the APOB gene disrupt the normal function of lipoprotein particles, which are responsible for transporting cholesterol in the blood. These mutations result in the production of defective LDL receptors, leading to the accumulation of LDL cholesterol in the bloodstream.

In addition to FH, OMIM contains information on many other genetic diseases. The catalog includes names of the genes associated with these diseases and provides detailed scientific and genetic information about each condition.

The Catalog of Genes and Diseases from OMIM is a valuable resource for researchers, healthcare professionals, and individuals looking to learn more about genetic conditions and their inheritance patterns. It offers support for patient advocacy and provides information on clinical trials and studies, making it a useful tool for advancing research in the field of genetics.

Citation: OMIM: Catalog of Genes and Diseases (https://omim.org)

Scientific Articles on PubMed

If you are interested in learning more about familial hypercholesterolemia, there are numerous scientific articles available on PubMed. These articles provide valuable information about the genetics, causes, and inheritance of this condition, as well as resources for support and advocacy.

One important gene associated with familial hypercholesterolemia is LDLRAP1, which plays a role in the normal function of low-density lipoprotein receptors. Mutations in this gene can lead to high levels of LDL cholesterol in the blood.

Research conducted at the Center for Genomic Medicine in Seattle has identified other genes, such as APOB, that can also cause familial hypercholesterolemia. These genes are involved in the production of proteins that transport lipoproteins through the bloodstream.

Several clinical trials listed on ClinicalTrials.gov are investigating new treatments and testing strategies for familial hypercholesterolemia. These trials aim to improve our understanding of the condition and find better ways to manage it.

Scientific articles on PubMed provide a wealth of information about familial hypercholesterolemia and related cardiovascular diseases. They cover topics such as the clinical presentation of the condition, diagnostic testing, treatment options, and the impact of familial hypercholesterolemia on overall health.

These articles can be an invaluable resource for healthcare professionals, researchers, and individuals affected by familial hypercholesterolemia. They offer up-to-date information and insights into the latest research findings.

For those interested in delving deeper into the scientific literature, PubMed provides a comprehensive database of articles on familial hypercholesterolemia. The articles are categorized by topic, making it easy to find relevant information.

In addition to scientific articles, resources like OMIM (Online Mendelian Inheritance in Man) provide detailed information about specific familial hypercholesterolemia genes and their functions.

If you are a patient or a parent of a person with familial hypercholesterolemia, it is important to stay informed about the latest research and treatment options. The information provided in scientific articles can help guide discussions with healthcare providers and make informed decisions about managing the condition.

References:

  • Zimmern R, et al. (2015). Familial Hypercholesterolemia. In: Pagon RA, et al., editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK174884/.

References

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