ANGPTL3 gene variants in subjects with familial combined hyperlipidemia.

Autor: Bea AM; Unidad de Lípidos, IIS Aragón, CIBERCV, Hospital Universitario Miguel Servet, Avda. Isabel La Católica 1-3, 50009, Zaragoza, Spain., Franco-Marín E; Unidad de Lípidos, IIS Aragón, CIBERCV, Hospital Universitario Miguel Servet, Avda. Isabel La Católica 1-3, 50009, Zaragoza, Spain., Marco-Benedí V; Unidad de Lípidos, IIS Aragón, CIBERCV, Hospital Universitario Miguel Servet, Avda. Isabel La Católica 1-3, 50009, Zaragoza, Spain.; Universidad de Zaragoza, Zaragoza, Spain., Jarauta E; Unidad de Lípidos, IIS Aragón, CIBERCV, Hospital Universitario Miguel Servet, Avda. Isabel La Católica 1-3, 50009, Zaragoza, Spain.; Universidad de Zaragoza, Zaragoza, Spain., Gracia-Rubio I; Unidad de Lípidos, IIS Aragón, CIBERCV, Hospital Universitario Miguel Servet, Avda. Isabel La Católica 1-3, 50009, Zaragoza, Spain., Cenarro A; Unidad de Lípidos, IIS Aragón, CIBERCV, Hospital Universitario Miguel Servet, Avda. Isabel La Católica 1-3, 50009, Zaragoza, Spain. ana.cenarro@gmail.com.; Instituto Aragonés de Ciencias de la Salud (IACS), Zaragoza, Spain. ana.cenarro@gmail.com., Civeira F; Unidad de Lípidos, IIS Aragón, CIBERCV, Hospital Universitario Miguel Servet, Avda. Isabel La Católica 1-3, 50009, Zaragoza, Spain.; Universidad de Zaragoza, Zaragoza, Spain., Lamiquiz-Moneo I; Unidad de Lípidos, IIS Aragón, CIBERCV, Hospital Universitario Miguel Servet, Avda. Isabel La Católica 1-3, 50009, Zaragoza, Spain.; Universidad de Zaragoza, Zaragoza, Spain.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2021 Mar 26; Vol. 11 (1), pp. 7002. Date of Electronic Publication: 2021 Mar 26.
DOI: 10.1038/s41598-021-86384-y
Abstrakt: Angiopoietin-like 3 (ANGPTL3) plays an important role in lipid metabolism in humans. Loss-of-function variants in ANGPTL3 cause a monogenic disease named familial combined hypolipidemia. However, the potential contribution of ANGPTL3 gene in subjects with familial combined hyperlipidemia (FCHL) has not been studied. For that reason, the aim of this work was to investigate the potential contribution of ANGPTL3 in the aetiology of FCHL by identifying gain-of-function (GOF) genetic variants in the ANGPTL3 gene in FCHL subjects. ANGPTL3 gene was sequenced in 162 unrelated subjects with severe FCHL and 165 normolipemic controls. Pathogenicity of genetic variants was predicted with PredictSNP2 and FruitFly. Frequency of identified variants in FCHL was compared with that of normolipemic controls and that described in the 1000 Genomes Project. No GOF mutations in ANGPTL3 were present in subjects with FCHL. Four variants were identified in FCHL subjects, showing a different frequency from that observed in normolipemic controls: c.607-109T>C, c.607-47_607-46delGT, c.835+41C>A and c.*52_*60del. This last variant, c.*52_*60del, is a microRNA associated sequence in the 3'UTR of ANGPTL3, and it was present 2.7 times more frequently in normolipemic controls than in FCHL subjects. Our research shows that no GOF mutations in ANGPTL3 were found in a large group of unrelated subjects with FCHL.
Databáze: MEDLINE
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