Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.18/1805
Título: Novel functional APOB mutations outside LDL-binding region causing familial hypercholesterolaemia
Autor: Alves, Ana Catarina
Etxebarria, Aitor
Soutar, Anne Katherine
Martin, Cesar
Bourbon, Mafalda
Palavras-chave: Doenças Cardio e Cérebro-vasculares
Familial Hypercholesterolaemia
Cholesterol
Low-Density Lipoprotein
Data: 13-Nov-2013
Editora: Oxford University Press
Citação: Hum Mol Genet. 2014 Apr 1;23(7):1817-28. doi: 10.1093/hmg/ddt573. Epub 2013 Nov 13
Resumo: Familial hypercholesterolaemia (FH) is characterized by increased circulating low-density lipoprotein (LDL) cholesterol leading to premature atherosclerosis and coronary heart disease. Although FH is usually caused by mutations in LDLR, mutations in APOB and PCSK9 also cause FH but only a few mutations have been reported, APOB p.R3527Q being the most common. However, 30-80% of clinical FH patients do not present an identifiable mutation in any of the described genes. To identify the genetic cause of the hypercholesterolaemia in 65 patients without mutations in LDLR, PCSK9 or in fragments of exon 26 and 29 of APOB currently analysed, we performed whole sequencing of APOB by pyrosequencing. A total of 10 putative mutations in APOB were identified. Flow cytometry with fluorescently labelled LDL from patients and relatives showed that p.Arg1164Thr (exon 22) and p.Gln4494del (exon 29) presented a 40% decrease in internalization in lymphocytes and HepG2 cells, very similar to APOB3527. The proliferation assays with U937 cells showed reduced growth for both cases. The variant p.Tyr1247Cys was found to be neutral and other three alterations were considered polymorphisms. Our results emphasize the need to study the whole APOB in routine protocols to improve patient identification and cardiovascular risk assessment.
Descrição: Ana Catarina Alves, colaboradora do grupo de investigação cardiovascular do Departamento da Promoção da Saúde e Prevenção de Doenças Não Transmissíveis do INSA, IP e aluna de doutoramento da Faculdade de Ciências da Universidade de Lisboa recebeu com este estudo, no dia 2 de junho de 2014, o Prémio Jovem Investigador atribuído pela Sociedade Europeia de Aterosclerose.
Peer review: yes
URI: http://hdl.handle.net/10400.18/1805
ISSN: ESSN 1460-2083
ISSN 0964-6906
Versão do Editor: http://hmg.oxfordjournals.org/content/early/2013/11/27/hmg.ddt573.abstract
Aparece nas colecções:DPSPDNT - Artigos em revistas internacionais

Ficheiros deste registo:
Ficheiro Descrição TamanhoFormato 
Novel functional APOB mutations.pdf395,55 kBAdobe PDFVer/Abrir    Acesso Restrito. Solicitar cópia ao autor!


FacebookTwitterDeliciousLinkedInDiggGoogle BookmarksMySpace
Formato BibTex MendeleyEndnote Degois 

Todos os registos no repositório estão protegidos por leis de copyright, com todos os direitos reservados.