Genetics of Familial Hypercholesterolemia

Brautbar, Ariel; Leary, Emili; Rasmussen, Kristen; Wilson, Don P.; Steiner, Robert D.; Virani, Salim S.

doi:10.1007/s11883-015-0491-z

Cited by 75 publications

(79 citation statements)

References 126 publications

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“…40,41 Therefore, it may be beneficial to undertake sequencing of the entire APOB gene because other rare variants in the gene may be responsible for the patient's clinical phenotype. 36,39 In the present study, we screened the whole exons in APOB and found some mutations in nonhot region. The hot exon of 26 showed a frequency of 37.8% in APOB mutations.…”

Section: Et Al Familial Hypercholesterolemia In China 577mentioning

confidence: 96%

“…34,38 The elevated prevalence of APOB mutations among Chinese patients might be possible, as pointed out by Andersen et al 38 Additionally, most currently available genetic testing in APOB is focused on exon 26 and p.Arg3500Trp rather than on the entire coding region. 39 Of note, there are case studies reporting mutations in the non-hot spot of APOB. 40,41 Therefore, it may be beneficial to undertake sequencing of the entire APOB gene because other rare variants in the gene may be responsible for the patient's clinical phenotype.…”

Section: Et Al Familial Hypercholesterolemia In China 577mentioning

confidence: 99%

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Familial Hypercholesterolemia Phenotype in Chinese Patients Undergoing Coronary Angiography

Zhu

et al. 2017

ATVB

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Large-scale clinical studies of FH have been reported from many countries, 2,7-16 but the features of FH in China are largely unknown. 17 Furthermore, the actual prevalence of FH is likely to be underestimated in the past, and the FH trait is masked by the CAD phenotype or more common risk factors without the genetically elevated cholesterol levels.3 Hence, the aim of present study was to investigate patients with FH phenotype and further provide molecular data on mutations for patients with FH in the Division of Dyslipidemia of Fu Wai Hospital, the only national center of dyslipidemia in China.© 2016 American Heart Association, Inc. Objective-Familial hypercholesterolemia (FH) is characterized by an elevated low-density lipoprotein cholesterol and increased risk of premature coronary artery disease. However, the general picture and mutational spectrum of FH in China are far from recognized, representing a missed opportunity for the investigation. Approach and Results-A total of 8050 patients undergoing coronary angiography were enrolled. The diagnosis of clinical FH was made using Dutch Lipid Clinic Network criteria, and the information of relatives was obtained by inquiring for the probands or from their own medical records of certain clinics/hospitals. Molecular analysis of FH was performed using target exome sequencing in LDLR (low-density lipoprotein cholesterol receptor gene), APOB (apolipoprotein B gene), and PCSK9 (proprotein convertase subtilisin/kexin type 9 gene). As a result, 3.5% of the patients with definite/ probable FH phenotype (definite 1.0% and probable 2.5%) were identified. Women FH had fewer premature coronary artery disease (women <60, or men <55 years of age) when compared with men FH (70.6% versus 82.7%; P<0.001), whereas angiographic extension of coronary artery disease was significantly increased with FH diagnosis in both men and women (P<0.001). Patterns of medication use in definite/probable FH were as follows: nontreated, 20.6%; low intensity, 6.0%; moderate intensity, 68.3%; and high intensity, 5.0%. However, none of them had achieved the lowdensity lipoprotein cholesterol <100 mg/dL. Additionally, mutational analysis was performed in 245 definite/probable FH cases, and risk variants were identified in 115 patients, giving a detection rate of 46.9%. Conclusions-We showed firsthand a common identification but poor treatment of patients with FH phenotype in Chinese coronary angiography patients. Genetic data in our FH cases might contribute to update the frequency and spectrum of Chinese FH scenarios. Materials and MethodsMaterials and Methods are available in the online-only Data Supplement. Results Prevalence of FHBasic characteristics of the study population are summarized in Table 1. The mean (±SD) age of the participants was 57.2±10.5 years, of whom 68.7% were men and 83.8% were with CAD and 37.8% with pCAD (<55 years for men and <60 years for women). The mean total cholesterol and LDL-C were 165.25±50.58 and 101.54±43.63 mg/dL, respectively. In the sample, there were 1.0% def...

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Section: Et Al Familial Hypercholesterolemia In China 577mentioning

confidence: 96%

Section: Et Al Familial Hypercholesterolemia In China 577mentioning

confidence: 99%

Familial Hypercholesterolemia Phenotype in Chinese Patients Undergoing Coronary Angiography

Zhu

et al. 2017

ATVB

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“…Overly narrow criteria may limit the review to a tiny subgroup of the affected patient population. For example, a review of the use of high‐dose omega‐3 fatty acid supplementation to prevent a second myocardial infarction in men aged 80 years or older with a history of prostate cancer and familial hypercholesterolemia would likely produce few studies and information useful for only a few patients because the prevalence of familial hypercholesterolemia is only about 0.2–0.5%, and the search criteria would produce a small subset of that group . Conversely, overly broad criteria may render the review results clinically meaningless.…”

Section: Methodsmentioning

confidence: 99%

Principles in the Evaluation of Systematic Reviews

2015

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Literature reviews summarize information from individual studies and are an important tool in the practice of evidence-based medicine. Various types of reviews, including narrative and systematic reviews, may be found within the biomedical literature. Systematic reviews are the strongest type and are often rated as the highest level of evidence. Thus it is important that clinicians understand how to evaluate them critically. This article is intended to enhance clinicians' understanding of the unique methods commonly used in systematic reviews by using the reporting standards to formulate evaluation principles. Explanations of the statistical tests and types of biases that are frequently encountered in systematic reviews are discussed. Lastly, an evaluation of a meta-analysis using these principles is provided.

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“…These polygenic influences alone (without any pathogenic mutation found in the classic 3 genes) can account for levels corresponding to homozygous FH (above 500 mg/dL) 80) . It has become clear that the genetics determining LDL-c levels is far more complex than originally believed with additional genes still being pursued 81) . As such, failure to detect a mutation does not exclude a diagnosis of FH, particularly if the clinical phenotype is highly suggestive of FH 76,78,82) .…”

Section: Hybrid Modelmentioning

confidence: 99%

Cascade Screening in Familial Hypercholesterolemia: Advancing Forward

Santos

Frauches

Chacra

2015

J Atheroscler Thromb

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Familial hypercholesterolemia is a genetic disorder associated with elevated LDL-cholesterol and high lifetime cardiovascular risk. Both clinical and molecular cascade screening programs have been implemented to increase early definition and treatment. In this systematic review, we discuss the main issues found in 65 different articles related to cascade screening and familial hypercholesterolemia, covering a range of topics including different types/strategies, considerations both positive and negative regarding cascade screening in general and associated with the different strategies, cost and coverage consideration, direct and indirect contact with patients, public policy around life insurance and doctor -patient confidentiality, the "right to know," and public health concerns regarding familial hypercholesterolemia.J Atheroscler Thromb, 2015; 22: 869-880.

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Genetics of Familial Hypercholesterolemia

Cited by 75 publications

References 126 publications

Familial Hypercholesterolemia Phenotype in Chinese Patients Undergoing Coronary Angiography

Familial Hypercholesterolemia Phenotype in Chinese Patients Undergoing Coronary Angiography

Principles in the Evaluation of Systematic Reviews

Cascade Screening in Familial Hypercholesterolemia: Advancing Forward

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