000168716 001__ 168716
000168716 005__ 20260217214838.0
000168716 0247_ $$2doi$$a10.1016/s0022-2275(20)30181-4
000168716 0248_ $$2sideral$$a51914
000168716 037__ $$aART-2002-51914
000168716 041__ $$aeng
000168716 100__ $$0(orcid)0000-0001-5956-4319$$aMozas, Pilar$$uUniversidad de Zaragoza
000168716 245__ $$aA mutation (-49C>T) in the promoter of the low density lipoprotein receptor gene associated with familial hypercholesterolemia.
000168716 260__ $$c2002
000168716 5060_ $$aAccess copy available to the general public$$fUnrestricted
000168716 5203_ $$aWe have identified a mutation (−49C>T) in the low-density lipoprotein receptor (LDLR) gene in a Spanish familial hypercholesterolemia (FH) patient. The mutation maps within repeat 3 of the LDLR gene promoter. This region binds Sp1 and collaborates with repeat 2 in the regulation of LDLR gene by sterols. To evaluate whether the mutation influenced the activity of the promoter, luciferase reporter plasmids containing 296 bp of the proximal promoter region were constructed. In transient transfection assays in HepG2 cells, the mutation resulted in an 80% reduction of promoter activity. Also, gel-shift assays demonstrated that the mutation severely affects Sp1 binding. However, the mutated promoter still retains the ability to respond to low sterol concentrations. As the analysis of the LDLR gene did not reveal any other changes, we conclude that the −49C>T mutation is the cause of FH in the patient. The analysis of the proband's pedigree indicated that not all the members of the family having the mutation disclose a FH phenotype. These results support the view that factors other than the presence of the mutation are important in the determination of the clinical phenotype in FH.
000168716 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttps://creativecommons.org/licenses/by/4.0/deed.es
000168716 590__ $$a3.73$$b2002
000168716 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b65 / 262 = 0.248$$c2002$$dQ1$$eT1
000168716 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000168716 700__ $$aGaletto, Roman
000168716 700__ $$aAlbajar, Marta
000168716 700__ $$aRos, Emilio
000168716 700__ $$0(orcid)0000-0001-8807-9187$$aPocovi, Miguel$$uUniversidad de Zaragoza
000168716 700__ $$aRodriguez Rey, Jose, C.
000168716 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000168716 773__ $$g43, 1 (2002), 13-18$$pJ. lipid res.$$tJournal of Lipid Research$$x0022-2275
000168716 8564_ $$s712169$$uhttps://zaguan.unizar.es/record/168716/files/texto_completo.pdf$$yVersión publicada
000168716 8564_ $$s2863613$$uhttps://zaguan.unizar.es/record/168716/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000168716 909CO $$ooai:zaguan.unizar.es:168716$$particulos$$pdriver
000168716 951__ $$a2026-02-17-20:14:06
000168716 980__ $$aARTICLE