000101617 001__ 101617 000101617 005__ 20240207145454.0 000101617 0247_ $$2doi$$a10.1038/s41598-021-86384-y 000101617 0248_ $$2sideral$$a123929 000101617 037__ $$aART-2021-123929 000101617 041__ $$aeng 000101617 100__ $$aBea, A.M. 000101617 245__ $$aANGPTL3 gene variants in subjects with familial combined hyperlipidemia 000101617 260__ $$c2021 000101617 5060_ $$aAccess copy available to the general public$$fUnrestricted 000101617 5203_ $$aAngiopoietin-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. 000101617 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/PI15-01983$$9info:eu-repo/grantAgreement/ES/ISCIII/PT17-0015-0039$$9info:eu-repo/grantAgreement/ES/DGA/B14-7R$$9info:eu-repo/grantAgreement/ES/MINECO/PI18-01777 000101617 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/ 000101617 590__ $$a4.997$$b2021 000101617 592__ $$a1.005$$b2021 000101617 591__ $$aMULTIDISCIPLINARY SCIENCES$$b19 / 74 = 0.257$$c2021$$dQ2$$eT1 000101617 593__ $$aMultidisciplinary$$c2021$$dQ1 000101617 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000101617 700__ $$aFranco-Marín, E. 000101617 700__ $$aMarco-Benedí, V.$$uUniversidad de Zaragoza 000101617 700__ $$0(orcid)0000-0001-9142-0737$$aJarauta, E.$$uUniversidad de Zaragoza 000101617 700__ $$aGracia-Rubio, I. 000101617 700__ $$aCenarro, A. 000101617 700__ $$0(orcid)0000-0001-7043-0952$$aCiveira, F.$$uUniversidad de Zaragoza 000101617 700__ $$0(orcid)0000-0002-9647-0108$$aLamiquiz-Moneo, I.$$uUniversidad de Zaragoza 000101617 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina 000101617 7102_ $$11003$$2027$$aUniversidad de Zaragoza$$bDpto. Anatom.Histolog.Humanas$$cArea Anatom.Embriol.Humana 000101617 773__ $$g11 (2021), 7002 [8 pp.]$$pSci. rep. (Nat. Publ. Group)$$tScientific reports (Nature Publishing Group)$$x2045-2322 000101617 8564_ $$s876378$$uhttps://zaguan.unizar.es/record/101617/files/texto_completo.pdf$$yVersión publicada 000101617 8564_ $$s2689856$$uhttps://zaguan.unizar.es/record/101617/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000101617 909CO $$ooai:zaguan.unizar.es:101617$$particulos$$pdriver 000101617 951__ $$a2024-02-07-14:51:50 000101617 980__ $$aARTICLE