Familial Hypercholesterolemia: The Most Frequent Cholesterol Metabolism Disorder Caused Disease

Benito‐Vicente, Asier; Uribe, Kepa B.; Jebari, Shifa; Galicia-García, Unai; Ostolaza, Helena; Martín, César

doi:10.3390/ijms19113426

Cited by 93 publications

(100 citation statements)

References 165 publications

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“…In more than 75% of cases of familial hypercholesterolemia, the LDL receptor is defective, owing to mutations in the LDLR gene. 9 Less often, the problem is a mutation in a gene for another molecule that interacts with the LDL receptor, such as apolipoprotein B (APOB), proprotein convertase subtilisin-kexin type 9 (PCSK9), or an unknown gene (Figure 1). 2,9 Because familial hypercholesterolemia is inherited in an autosomal dominant fashion, most patients who have it are heterozygous, possessing 1 normal allele and 1 mutated allele.…”

Section: ■ Mutations In Ldlr and Other Genesmentioning

confidence: 99%

“…9 Less often, the problem is a mutation in a gene for another molecule that interacts with the LDL receptor, such as apolipoprotein B (APOB), proprotein convertase subtilisin-kexin type 9 (PCSK9), or an unknown gene (Figure 1). 2,9 Because familial hypercholesterolemia is inherited in an autosomal dominant fashion, most patients who have it are heterozygous, possessing 1 normal allele and 1 mutated allele. 10 The prevalence of heterozygous familial hypercholesterolemia is about 1 in 220, based on large genetic studies.…”

Section: ■ Mutations In Ldlr and Other Genesmentioning

confidence: 99%

“…Several mutations remain unknown, and not finding a genetic mutation does not exclude the diagnosis, especially if there is strong phenotypic evidence. 9 Finding a mutation also has prognostic value. At any LDL-C level, a gene-positive individual carries a higher risk of atherosclerotic cardiovascular disease than does a genenegative one.…”

Section: ■ Genetic Testing Is the Gold Standardmentioning

confidence: 99%

“…Reducing LDL-C levels is the primary goal, and high-dose statins are the first-line treatment. Statins inhibit the enzyme 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, resulting in decreased cholesterol production and increased LDL receptor expression on the surface of hepatocytes, which further reduces plasma LDL-C. 9 Statin therapy should be started as soon as possible to help prevent cardiovascular events. In homozygous familial hypercholesterolemia patients, statin therapy is often started in the first decade of life.…”

Section: Statins Are the First-line Treatmentmentioning

confidence: 99%

“…50 Ezetimibe is a selective cholesterol absorption inhibitor that blocks uptake of cholesterol at both the enterocyte lumen and the hepatobiliary system. 9 This leads to depletion of cholesterol stores and increased expression of LDL receptor, which further reduces plasma LDL-C. 9 In patients already taking a statin, ezetimibe can further reduce LDL-C by 15% to 20% and is generally well tolerated in combination with statin therapy. 1,51 National and international guidelines suggest ezetimibe as a second-line agent when LDL-C goals are not met with statins alone.…”

Section: Statins Are the First-line Treatmentmentioning

confidence: 99%

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Familial hypercholesterolemia: Detect, treat, and ask about family

Shah

Ahmed

Tang³

2020

CCJM

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Section: ■ Mutations In Ldlr and Other Genesmentioning

confidence: 99%

Section: ■ Mutations In Ldlr and Other Genesmentioning

confidence: 99%

Section: ■ Genetic Testing Is the Gold Standardmentioning

confidence: 99%

Section: Statins Are the First-line Treatmentmentioning

confidence: 99%

Section: Statins Are the First-line Treatmentmentioning

confidence: 99%

See 3 more Smart Citations

Familial hypercholesterolemia: Detect, treat, and ask about family

Shah

Ahmed

Tang³

2020

CCJM

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Outcomes from a pilot genetic counseling intervention using motivational interviewing and the extended parallel process model to increase cascade cholesterol screening

Baldry

Redlinger‐Grosse

MacFarlane

et al. 2021

Journal of Genetic Counseling

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Familial hypercholesterolemia (FH) is an inherited condition resulting in increased risk of premature cardiovascular disease. This risk can be reduced with early diagnosis and treatment, but it can be challenging to identify individuals with FH. Cascade screening, the most efficient and cost‐effective identification method, requires FH patients to communicate with their at‐risk family and encourage them to pursue screening. Beyond FH, patients with conditions increasing disease risk to family members report barriers to the communication process such as insufficient knowledge of the condition and discomfort informing relatives. We conducted a pilot study of a genetic counseling intervention incorporating behavior‐change principles from motivational interviewing (MI) and the extended parallel process model (EPPM) to help parents of children with FH overcome these barriers and improve cascade screening rates for FH. Of the 13 participants who completed the intervention and post‐intervention surveys, 6 reported contacting and/or screening additional relatives. A large effect size in increasing communication and screening was observed (η2 = 0.20), with the mean percent of at‐risk relatives contacted rising from 33% to 45%, and the mean percent screened rising from 32% to 42%. On average, 2.23 new relatives were contacted and 2.46 were screened, per participant, by the end of the study. Direct content analysis revealed that despite the open‐ended nature of the goal‐setting process, participant goals fell into two categories including those who set goals focused on communicating with and screening family members (n = 9) and those who set goals only focused on managing FH (n = 4). Overall, the communication and screening rates reported after the intervention were higher than previous observations in adult FH populations. These results suggest this EPPM/MI genetic counseling intervention could be a useful tool for increasing communication and cascade screening for FH. With further research on goal‐setting techniques, the intervention could be refined and replicated to identify more individuals affected by FH or modified for use with other actionable genetic conditions.

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Compendium of causative genes and their encoded proteins for common monogenic disorders

Apgar

Sanders

2021

Protein Science

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A compendium is presented of inherited monogenic disorders that have a prevalence of >1:20,000 in the human population, along with their causative genes and encoded proteins. "Simple" monogenic diseases are those for which the clinical features are caused by mutations impacting a single gene, usually in a manner that alters the sequence of the encoded protein. Of course, for a given "monogenic disorder", there is sometimes more than one potential disease gene, mutations in any one of which is sufficient to cause phenotypes of that disorder. Disease-causing mutations for monogenic disorders are usually passed on from generation to generation in a Mendelian fashion, and originate from spontaneous (de novo) germline founder mutations. In the past monogenic disorders have often been written off as targets for drug discovery because they sometimes are assumed to be rare disorders, for which the meager projected financial payoff of drug discovery and development has discouraged investment. However, not all monogenic diseases are rare. Here, we report that that currently available data identifies 72 disorders with a prevalence of at least 1 in 20,000 humans. For each, we tabulate the gene(s) for which mutations cause the spectrum of phenotypes associated with that disorder. We also identify the gene and protein that most commonly causes each disease. 34 of these disorders are caused exclusively by mutations in only a single gene and encoded protein.

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Familial Hypercholesterolemia: The Most Frequent Cholesterol Metabolism Disorder Caused Disease

Cited by 93 publications

References 165 publications

Familial hypercholesterolemia: Detect, treat, and ask about family

Familial hypercholesterolemia: Detect, treat, and ask about family

Outcomes from a pilot genetic counseling intervention using motivational interviewing and the extended parallel process model to increase cascade cholesterol screening

Compendium of causative genes and their encoded proteins for common monogenic disorders

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