Abstract | Context:
Angiopoietin-like 3 (ANGPTL3) deficiency in plasma due to loss-of-function gene mutations results in familial combined hypobetalipoproteinemia type 2 ( FHBL2) in homozygotes. However, the lipid phenotype in heterozygotes is much milder and does not appear to relate directly to ANGPTL3 levels. Furthermore, the low-density lipoprotein ( LDL) phenotype in carriers of ANGPTL3 mutations is unexplained. Objective: Design: Results: Conclusions: Our results suggest that the hypolipidemic effects of ANGPTL3 mutations in FHBL2 are dependent on a threshold of plasma ANGPTL3 levels, with differential effects on various lipoprotein particles. The increased inactivation of PCSK9 by furin in FHBL1 and FHBL2 is likely to cause increased LDL clearance and suggests novel therapeutic avenues.
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Authors | Sergio Fazio, Jessica Minnier, Michael D Shapiro, Sotirios Tsimikas, Patrizia Tarugi, Maurizio R Averna, Marcello Arca, Hagai Tavori |
Journal | The Journal of clinical endocrinology and metabolism
(J Clin Endocrinol Metab)
Vol. 102
Issue 9
Pg. 3340-3348
(09 01 2017)
ISSN: 1945-7197 [Electronic] United States |
PMID | 28633452
(Publication Type: Comparative Study, Journal Article)
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Copyright | Copyright © 2017 Endocrine Society |
Chemical References |
- ANGPTL3 protein, human
- Angiopoietin-Like Protein 3
- Angiopoietin-like Proteins
- Angiopoietins
- Apolipoproteins B
- Lipoproteins, HDL
- Lipoproteins, LDL
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Topics |
- Adult
- Aged
- Angiopoietin-Like Protein 3
- Angiopoietin-like Proteins
- Angiopoietins
(genetics)
- Apolipoproteins B
(blood)
- Blotting, Western
- Cohort Studies
- Female
- Genetic Predisposition to Disease
- Heterozygote
- Humans
- Hypobetalipoproteinemias
(blood, genetics, physiopathology)
- Linear Models
- Lipoproteins, HDL
(blood)
- Lipoproteins, LDL
(blood)
- Male
- Middle Aged
- Multivariate Analysis
- Mutation
- Pedigree
- Phenotype
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