Identification of novel APOB mutations by targeted next-generation sequencing for the molecular diagnosis of familial hypobetalipoproteinemia

Rimbert, Antoine; Pichelin, Matthieu; Lecointe, Simon; Marrec, Marie; Scouarnec, Solena Le; Barrak, E.; Croyal, Mikaël; Krempf, Michel; Marec, Hervé Le; Redon, Richard; Schott, Jean‐Jacques; Magré, Jocelyne; Cariou, Bertrand

doi:10.1016/j.atherosclerosis.2016.04.010

Cited by 17 publications

(21 citation statements)

References 24 publications

(31 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, the number of people, who met the phenotypic criteria, could not be very large. However, the number of our study subjects was relatively large, compared with those in other studies,[ 4 ] particularly studies conducted with respect to Asian ethnicities. Finally, because of the study design and inclusion criteria, the range of LDL-C levels was quite narrow in our study.…”

Section: Discussionmentioning

confidence: 91%

“…In previous studies, the prevalence of APOB mutations in hypobetalipoproteinemia ranged from 44% to 64%. [ 4 , 16 , 17 ] However, genetic data for this disease in Asian patients has been scarce. The prevalence of rare variants in APOB , detected in our study, was 41%, which indicates a lower tendency than that in Western studies.…”

Section: Discussionmentioning

confidence: 99%

“…[ 1 – 3 ] Additionally, they can show LDL-C levels <5 percentile or <50 mg/dL without lipid-lowering therapy. [ 4 ] In patients with homozygous variants, LDL-C levels are known to be much lower. Although the patients are often asymptomatic, some have increased risk for steatohepatitis.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Rare and common variants of APOB and PCSK9 in Korean patients with extremely low low-density lipoprotein-cholesterol levels

et al. 2017

View full text Add to dashboard Cite

BackgroundScreening of variants, related to lipid metabolism in patients with extreme cholesterol levels, is a tool used to identify targets affecting cardiovascular outcomes. The aim of this study was to examine the prevalence and characteristics of rare and common variants of APOB and PCSK9 in Korean patients with extremely low low-density lipoprotein-cholesterol (LDL-C) levels.MethodsAmong 13,545 participants enrolled in a cardiovascular genome cohort, 22 subjects, whose LDL-C levels without lipid-lowering agents were ≤1 percentile (48 mg/dL) of Korean population, were analyzed. Two target genes, APOB and PCSK9, were sequenced by targeted next-generation sequencing. Prediction of functional effects was conducted using SIFT, PolyPhen-2, and Mutation Taster, and matched against a public database of variants.ResultsEight rare variants of the two candidate genes (five in APOB and three in PCSK9) were found in nine subjects. Two subjects had more than two different rare variants of either gene (one subject in APOB and another subject in APOB/PCSK9). Conversely, 12 common variants (nine in APOB and three in PCSK9) were discovered in 21 subjects. Among all variants, six in APOB and three in PCSK9 were novel. Several variants previously reported functional, including c.C277T (p.R93C) and c.G2009A (p.G670E) of PCSK9, were found in our population.ConclusionsRare variants of APOB or PCSK9 were identified in nine of the 22 study patients with extremely low LDL-C levels, whereas most of them had common variants of the two genes. The common novelty of variants suggested polymorphism of the two genes among them. Our results provide rare genetic information associated with this lipid phenotype in East Asian people.

show abstract

Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Rare and common variants of APOB and PCSK9 in Korean patients with extremely low low-density lipoprotein-cholesterol levels

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Mutations in the genes investigated also contribute to monogenic dyslipidaemias. Deleterious mutations in LDLR are the most common cause of FH [8,45,46]; loss of function variants in LDLRAP1 have been documented to cause high LDL-cholesterol levels with a recessive form of inheritance (38); variants in APOB have been known to cause both low and high LDLcholesterol levels [16,[47][48][49]; and loss of function variants that cause low LDL-cholesterol have been identified in PCSK9 [50][51][52]. In this study, two LDLRAP1 variants were associated with low LDL-cholesterol levels.…”

Section: Discussionmentioning

confidence: 60%

Genetic associations between serum low LDL-cholesterol levels and variants in LDLR, APOB, PCSK9 and LDLRAP1 in African populations

et al. 2020

View full text Add to dashboard Cite

Non-communicable diseases, including cardiovascular diseases (CVDs), are increasing in African populations. High serum low density lipoprotein cholesterol (LDL-cholesterol) levels are a known risk factor for CVDs in European populations, but the link remains poorly understood among Africans. This study investigated the associations between serum LDL-cholesterol levels and selected variants in the low density lipoprotein receptor (LDLR), apolipoprotein B (APOB), proprotein convertase subtilisin/kexin type 9 (PCSK9) and low density lipoprotein receptor adaptor protein 1 (LDLRAP1) genes in some selected African populations. Nineteen SNPs were selected from publicly available African whole genome sequence data based on functional prediction and allele frequency. SNPs were genotyped in 1000 participants from the AWI-Gen, study selected from the extremes of LDL-cholesterol level distribution (500 with LDL-cholesterol>3.5 mmol/L and 500 with LDL-cholesterol<1.1 mmol/L). The minor alleles at five of the six associated SNPs were significantly associated (P<0.

show abstract

“…In a previous study aiming at identifying new genes in LDL-C metabolism, we recruited FHBL patients by screening the database of the Nantes University Hospital (HYPOCHOL study, NCT02354079) [ 7 ]. We were surprised to observe that ≈ 40% of patients were coming from the Psychiatry units, which were ranked first amongst the different clinical departments, even after excluding eating disorders.…”

Section: Introductionmentioning

confidence: 99%

Prevalence of hypobetalipoproteinemia and related psychiatric characteristics in a psychiatric population: results from the retrospective HYPOPSY Study

Cariou¹,

Challet-Bouju²,

Bernard³

et al. 2018

Lipids Health Dis

Self Cite

View full text Add to dashboard Cite

BackgroundHypobetalipoproteinemia (HBL) is defined by plasma concentrations of LDL-cholesterol (LDL-C) lower than the fifth percentile for age and sex. Several psychiatric symptoms have been reported in association with HBL. The objective was to assess the prevalence of primary HBL in patients hospitalized in a psychiatric population and to better characterize the related psychiatric disorders.MethodsHYPOPSY is a retrospective study including 839 adults hospitalized in the Psychiatry department of Nantes University Hospital during the year 2014, except patients with eating disorders. The prevalence of primary HBL was defined by a plasma LDL-C concentration ≤ 50 mg/dL. Secondary causes of HBL were excluded after a review of medical records (n=2). Related-psychiatric disorders in patients with and without HBL were recorded using the ICD-10 classification.ResultsTwenty cases of primary HBL (mean [SD] LDL-C: 42 [7] mg/dL) were diagnosed, leading to a prevalence of 2.39%. In comparison, the prevalence of HBL in a healthy control population was 0.57%. Psychiatric patients with HBL were characterized by a higher frequency of schizophrenia (p=0.044), hetero-aggression (p=0.015) and pervasive and specific developmental disorders (including autism) (p=0.011).ConclusionsThe prevalence of HBL is 4-fold higher in psychiatric than in general population. More specifically, some statistically significant associations were found between low LDL-C concentrations and schizophrenia, autism and hetero-aggression. These data reinforce the hypothesis for a link between genetically low LDL-C levels and psychiatric disorders.Electronic supplementary materialThe online version of this article (10.1186/s12944-018-0892-4) contains supplementary material, which is available to authorized users.

show abstract

Identification of novel APOB mutations by targeted next-generation sequencing for the molecular diagnosis of familial hypobetalipoproteinemia

Abstract: Our study further demonstrates that NGS is a reliable and practical approach for the molecular screening of FHBL-causative genes that may provide a mean for deciphering the genetic basis in FHBL.

Cited by 17 publications

References 24 publications

Rare and common variants of APOB and PCSK9 in Korean patients with extremely low low-density lipoprotein-cholesterol levels

Rare and common variants of APOB and PCSK9 in Korean patients with extremely low low-density lipoprotein-cholesterol levels

Genetic associations between serum low LDL-cholesterol levels and variants in LDLR, APOB, PCSK9 and LDLRAP1 in African populations

Prevalence of hypobetalipoproteinemia and related psychiatric characteristics in a psychiatric population: results from the retrospective HYPOPSY Study

Contact Info

Product

Resources

About