101617 20250520101728.0 doi 10.1038/s41598-021-86384-y sideral 123929 ART-2021-123929 eng Bea, A.M. ANGPTL3 gene variants in subjects with familial combined hyperlipidemia 2021 Access copy available to the general public Unrestricted 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. info:eu-repo/grantAgreement/ES/DGA/B14-7R info:eu-repo/grantAgreement/ES/ISCIII/PT17-0015-0039 info:eu-repo/grantAgreement/ES/MINECO/PI15-01983 info:eu-repo/grantAgreement/ES/MINECO/PI18-01777 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 4.997 2021 MULTIDISCIPLINARY SCIENCES 19 / 74 = 0.257 2021 Q2 T1 1.005 2021 Multidisciplinary 2021 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Franco-Marín, E. Marco-Benedí, V. Universidad de Zaragoza Jarauta, E. Universidad de Zaragoza (orcid)0000-0001-9142-0737 Gracia-Rubio, I. (orcid)0000-0003-1028-8581 Cenarro, A. Civeira, F. Universidad de Zaragoza (orcid)0000-0001-7043-0952 Lamiquiz-Moneo, I. Universidad de Zaragoza (orcid)0000-0002-9647-0108 1007 610 Universidad de Zaragoza Dpto. Medicina, Psiqu. y Derm. Area Medicina 1003 027 Universidad de Zaragoza Dpto. Anatom.Histolog.Humanas Area Anatom.Embriol.Humana 11 (2021), 7002 [8 pp.] Sci. rep. (Nat. Publ. Group) Scientific reports (Nature Publishing Group) 2045-2322 876378 http://zaguan.unizar.es/record/101617/files/texto_completo.pdf Versión publicada 2689856 http://zaguan.unizar.es/record/101617/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:101617 articulos driver 2025-05-20-10:13:57 ARTICLE