Clinical characteristics and plasma lipids in subjects with familial combined hypolipidemia: a pooled analysis

Angelo Baldassare Cefalu', Maurizio Averna, Giovanni Pigna, Ester Ciociola, Juan Antonio Arroyo, Ilenia Minicocci, Sebastiano Calandra, Sara Santini, Gertrudis Martí, Fabio Pannozzo, Nathan Stitziel, Sekar Kathiresan, Livia Pisciotta, Fabrizio Ceci, Marianna Maranghi, Vito Cantisani, Giancarlo Labbadia, Patrizia Tarugi, Stefano Bertolini, Marcello Arca

Risultato della ricerca: Article

24 Citazioni (Scopus)

Abstract

Angiopoietin-like 3 (ANGPTL3) regulates lipoprotein metabolism by modulating extracellular lipases. Loss-of function mutations in ANGPTL3 gene cause familial combined hypolipidemia (FHBL2). The mode of inheritance and hepatic and vascular consequences of FHBL2 have not been fully elucidated. To get further insights on these aspects, we reevaluated the clinical and the biochemical characteristics of all reported cases of FHBL2. One hundred fifteen FHBL2 individuals carrying 13 different mutations in the ANGPTL3 gene (14 homozygotes, 8 compound heterozygotes, and 93 heterozygotes) and 402 controls were considered. Carriers of two mutant alleles had undetectable plasma levels of ANGPTL3 protein, whereas heterozygotes showed a reduction ranging from 34% to 88%, according to genotype. Compared with controls, homozygotes as well as heterozygotes showed a significant reduction of all plasma lipoproteins, while no difference in lipoprotein(a) [Lp(a)] levels was detected between groups. The prevalence of fatty liver was not different in FHBL2 subjects compared with controls. Notably, diabetes mellitus and cardiovascular disease were absent among homozygotes. FHBL2 trait is inherited in a codominant manner, and the lipid-lowering effect of two ANGPTL3 mutant alleles was more than four times larger than that of one mutant allele. No changes in Lp(a) were detected in FHBL2. Furthermore, our analysis confirmed that FHBL2 is not associated with adverse clinical sequelae. The possibility that FHBL2 confers lower risk of diabetes and cardiovascular disease warrants more detailed investigation.
Lingua originaleEnglish
pagine (da-a)3481-3490
Numero di pagine10
RivistaJournal of Lipid Research
Volume54
Stato di pubblicazionePublished - 2013

Fingerprint

Angiopoietins
Heterozygote
Lipids
Plasmas
Homozygote
Lipoprotein(a)
Alleles
Medical problems
Lipoproteins
Cardiovascular Diseases
Genes
Mutation
Fatty Liver
Lipase
Metabolism
Liver
Blood Vessels
Diabetes Mellitus
Genotype
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Endocrinology
  • Cell Biology

Cita questo

Clinical characteristics and plasma lipids in subjects with familial combined hypolipidemia: a pooled analysis. / Cefalu', Angelo Baldassare; Averna, Maurizio; Pigna, Giovanni; Ciociola, Ester; Arroyo, Juan Antonio; Minicocci, Ilenia; Calandra, Sebastiano; Santini, Sara; Martí, Gertrudis; Pannozzo, Fabio; Stitziel, Nathan; Kathiresan, Sekar; Pisciotta, Livia; Ceci, Fabrizio; Maranghi, Marianna; Cantisani, Vito; Labbadia, Giancarlo; Tarugi, Patrizia; Bertolini, Stefano; Arca, Marcello.

In: Journal of Lipid Research, Vol. 54, 2013, pag. 3481-3490.

Risultato della ricerca: Article

Cefalu', AB, Averna, M, Pigna, G, Ciociola, E, Arroyo, JA, Minicocci, I, Calandra, S, Santini, S, Martí, G, Pannozzo, F, Stitziel, N, Kathiresan, S, Pisciotta, L, Ceci, F, Maranghi, M, Cantisani, V, Labbadia, G, Tarugi, P, Bertolini, S & Arca, M 2013, 'Clinical characteristics and plasma lipids in subjects with familial combined hypolipidemia: a pooled analysis', Journal of Lipid Research, vol. 54, pagg. 3481-3490.
Cefalu', Angelo Baldassare ; Averna, Maurizio ; Pigna, Giovanni ; Ciociola, Ester ; Arroyo, Juan Antonio ; Minicocci, Ilenia ; Calandra, Sebastiano ; Santini, Sara ; Martí, Gertrudis ; Pannozzo, Fabio ; Stitziel, Nathan ; Kathiresan, Sekar ; Pisciotta, Livia ; Ceci, Fabrizio ; Maranghi, Marianna ; Cantisani, Vito ; Labbadia, Giancarlo ; Tarugi, Patrizia ; Bertolini, Stefano ; Arca, Marcello. / Clinical characteristics and plasma lipids in subjects with familial combined hypolipidemia: a pooled analysis. In: Journal of Lipid Research. 2013 ; Vol. 54. pagg. 3481-3490.
@article{0afc44ae7627471eaa537b0655fdd0ba,
title = "Clinical characteristics and plasma lipids in subjects with familial combined hypolipidemia: a pooled analysis",
abstract = "Angiopoietin-like 3 (ANGPTL3) regulates lipoprotein metabolism by modulating extracellular lipases. Loss-of function mutations in ANGPTL3 gene cause familial combined hypolipidemia (FHBL2). The mode of inheritance and hepatic and vascular consequences of FHBL2 have not been fully elucidated. To get further insights on these aspects, we reevaluated the clinical and the biochemical characteristics of all reported cases of FHBL2. One hundred fifteen FHBL2 individuals carrying 13 different mutations in the ANGPTL3 gene (14 homozygotes, 8 compound heterozygotes, and 93 heterozygotes) and 402 controls were considered. Carriers of two mutant alleles had undetectable plasma levels of ANGPTL3 protein, whereas heterozygotes showed a reduction ranging from 34{\%} to 88{\%}, according to genotype. Compared with controls, homozygotes as well as heterozygotes showed a significant reduction of all plasma lipoproteins, while no difference in lipoprotein(a) [Lp(a)] levels was detected between groups. The prevalence of fatty liver was not different in FHBL2 subjects compared with controls. Notably, diabetes mellitus and cardiovascular disease were absent among homozygotes. FHBL2 trait is inherited in a codominant manner, and the lipid-lowering effect of two ANGPTL3 mutant alleles was more than four times larger than that of one mutant allele. No changes in Lp(a) were detected in FHBL2. Furthermore, our analysis confirmed that FHBL2 is not associated with adverse clinical sequelae. The possibility that FHBL2 confers lower risk of diabetes and cardiovascular disease warrants more detailed investigation.",
author = "Cefalu', {Angelo Baldassare} and Maurizio Averna and Giovanni Pigna and Ester Ciociola and Arroyo, {Juan Antonio} and Ilenia Minicocci and Sebastiano Calandra and Sara Santini and Gertrudis Mart{\'i} and Fabio Pannozzo and Nathan Stitziel and Sekar Kathiresan and Livia Pisciotta and Fabrizio Ceci and Marianna Maranghi and Vito Cantisani and Giancarlo Labbadia and Patrizia Tarugi and Stefano Bertolini and Marcello Arca",
year = "2013",
language = "English",
volume = "54",
pages = "3481--3490",
journal = "Journal of Lipid Research",
issn = "0022-2275",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",

}

TY - JOUR

T1 - Clinical characteristics and plasma lipids in subjects with familial combined hypolipidemia: a pooled analysis

AU - Cefalu', Angelo Baldassare

AU - Averna, Maurizio

AU - Pigna, Giovanni

AU - Ciociola, Ester

AU - Arroyo, Juan Antonio

AU - Minicocci, Ilenia

AU - Calandra, Sebastiano

AU - Santini, Sara

AU - Martí, Gertrudis

AU - Pannozzo, Fabio

AU - Stitziel, Nathan

AU - Kathiresan, Sekar

AU - Pisciotta, Livia

AU - Ceci, Fabrizio

AU - Maranghi, Marianna

AU - Cantisani, Vito

AU - Labbadia, Giancarlo

AU - Tarugi, Patrizia

AU - Bertolini, Stefano

AU - Arca, Marcello

PY - 2013

Y1 - 2013

N2 - Angiopoietin-like 3 (ANGPTL3) regulates lipoprotein metabolism by modulating extracellular lipases. Loss-of function mutations in ANGPTL3 gene cause familial combined hypolipidemia (FHBL2). The mode of inheritance and hepatic and vascular consequences of FHBL2 have not been fully elucidated. To get further insights on these aspects, we reevaluated the clinical and the biochemical characteristics of all reported cases of FHBL2. One hundred fifteen FHBL2 individuals carrying 13 different mutations in the ANGPTL3 gene (14 homozygotes, 8 compound heterozygotes, and 93 heterozygotes) and 402 controls were considered. Carriers of two mutant alleles had undetectable plasma levels of ANGPTL3 protein, whereas heterozygotes showed a reduction ranging from 34% to 88%, according to genotype. Compared with controls, homozygotes as well as heterozygotes showed a significant reduction of all plasma lipoproteins, while no difference in lipoprotein(a) [Lp(a)] levels was detected between groups. The prevalence of fatty liver was not different in FHBL2 subjects compared with controls. Notably, diabetes mellitus and cardiovascular disease were absent among homozygotes. FHBL2 trait is inherited in a codominant manner, and the lipid-lowering effect of two ANGPTL3 mutant alleles was more than four times larger than that of one mutant allele. No changes in Lp(a) were detected in FHBL2. Furthermore, our analysis confirmed that FHBL2 is not associated with adverse clinical sequelae. The possibility that FHBL2 confers lower risk of diabetes and cardiovascular disease warrants more detailed investigation.

AB - Angiopoietin-like 3 (ANGPTL3) regulates lipoprotein metabolism by modulating extracellular lipases. Loss-of function mutations in ANGPTL3 gene cause familial combined hypolipidemia (FHBL2). The mode of inheritance and hepatic and vascular consequences of FHBL2 have not been fully elucidated. To get further insights on these aspects, we reevaluated the clinical and the biochemical characteristics of all reported cases of FHBL2. One hundred fifteen FHBL2 individuals carrying 13 different mutations in the ANGPTL3 gene (14 homozygotes, 8 compound heterozygotes, and 93 heterozygotes) and 402 controls were considered. Carriers of two mutant alleles had undetectable plasma levels of ANGPTL3 protein, whereas heterozygotes showed a reduction ranging from 34% to 88%, according to genotype. Compared with controls, homozygotes as well as heterozygotes showed a significant reduction of all plasma lipoproteins, while no difference in lipoprotein(a) [Lp(a)] levels was detected between groups. The prevalence of fatty liver was not different in FHBL2 subjects compared with controls. Notably, diabetes mellitus and cardiovascular disease were absent among homozygotes. FHBL2 trait is inherited in a codominant manner, and the lipid-lowering effect of two ANGPTL3 mutant alleles was more than four times larger than that of one mutant allele. No changes in Lp(a) were detected in FHBL2. Furthermore, our analysis confirmed that FHBL2 is not associated with adverse clinical sequelae. The possibility that FHBL2 confers lower risk of diabetes and cardiovascular disease warrants more detailed investigation.

UR - http://hdl.handle.net/10447/94463

M3 - Article

VL - 54

SP - 3481

EP - 3490

JO - Journal of Lipid Research

JF - Journal of Lipid Research

SN - 0022-2275

ER -