Repositório Científico do Instituto Nacional de Saúde >
Departamento de Promoção da Saúde e Prevenção de Doenças Não Transmissíveis >
DPSPDNT - Posters/abstracts em congressos internacionais >

Please use this identifier to cite or link to this item: http://hdl.handle.net/10400.18/388

Título: Genetic basis of familial hypercholesterolaemia
Autor: Alves, A.C.
Bourbon, M.
Palavras-chave: Doenças Cardio e Cérebro-vasculares
Issue Date: Oct-2011
Editora: Instituto Nacional de Saúde Doutor Ricardo Jorge, IP
Resumo: Familial hypercholesterolemia (FH) is a genetic condition characterized by a high cholesterol concentration in the blood. The most frequent causes of FH are inherited defects in the Low Density Lipoprotein Receptor gene (LDLR) but, in a small percentage of patients, mutations in the apolipoprotein B gene (APOB) and in the propotein convertase subtilisin/kexin type 9 gene (PCSK9) are also responsible for FH. These 3 genes are currently studied in the “Portuguese FH study”. From the 404 families with a clinical diagnosis of FH already studied only 48% of these have a mutation in one of the 3 studied genes, so other gene defects must exist to explain the cause of hypercholesterolemia in the remaining families. The first aim was the exclusion of previously unidentified LDLR and APOB gene defects, as well as the exclusion of mutations in LDLRAP1 and CYP7A1 genes in patients with possible recessive hypercholesterolemia. A second aim was the whole sequencing of APOB gene, in 65 index patients without mutations in LDLR or PCSK9 genes or in fragments of exon 26 and 29 of APOB gene, by pyrosequencing, in order to identify the genetic cause of the hypercholesterolemia in these patients. CYP7A1 and LDLRAP1 genes were analysed by PCR and direct sequencing. A pool of the 65 DNAs was sequenced by pyrosequecing method and a total of 227688 nucleotide reads were obtained, corresponding to a mean coverage of 35x/fragment/individual. No mutations were found in LDLRAP1 and CYP7A1 genes in 10 patients with possible recessive hypercholesterolemia. A total of 87 alterations were detected, being 27 described SNPs. From the 26 alterations detected, only 12 were found and 4 of these had not been previously described. After family studies only one alteration did not co-segregate in the family, providing further evidence that 3 of the alterations found can be mutations causing disease, but functional studies are required to prove pathogenicity. Patients, in whom it was not possible to find the genetic cause of the hypercholesterolaemia, will continue to be studied, since all show a severe clinical phenotype of FH.
URI: http://hdl.handle.net/10400.18/388
Appears in Collections:DPSPDNT - Posters/abstracts em congressos internacionais

Files in This Item:

File Description SizeFormat
Genetic basis of familial hypercholesterolaemia.pdf879,84 kBAdobe PDFView/Open
Restrict Access. You can request a copy!
Statistics
FacebookTwitterDeliciousLinkedInDiggGoogle BookmarksMySpaceOrkut
Formato BibTex mendeley Endnote Logotipo do DeGóis 

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

 

  © 2010 www.insa.pt - Todos os direitos reservados | Feedback Ministério da Saúde
Promotores do RCAAP   Financiadores do RCAAP

Fundação para a Ciência e a Tecnologia Universidade do Minho   Governo Português Ministério da Educação e Ciência PO Sociedade do Conhecimento (POSC) Portal oficial da União Europeia