Repositório Científico do Instituto Nacional de Saúde >
Departamento de Genética Humana >
DGH - Posters/abstracts em congressos nacionais >

Please use this identifier to cite or link to this item: http://hdl.handle.net/10400.18/401

Título: Hepcidin Gene Promoter c.-1010T and c.-582G Variants are Modulators of Iron Overload Development in Individuals Carrying the H63D Mutation in the HFE Gene
Autor: Silva, Bruno
Pita, Lina
Gomes, Susana
Gonçalves, João
Faustino, Paula
Palavras-chave: Hepcidin
HFE
SNPs
Iron overload
Doenças Genéticas
Issue Date: Nov-2011
Editora: Instituto Nacional de Saúde Doutor Ricardo Jorge, IP
Resumo: Mutated HFE gene/protein is usually associated with Hereditary Hemochromatosis (HH). Despite C282Y being the most common HH-associated HFE mutation, others, such as H63D, also have an uncertain role in the pathogenesis of HH. Hepcidin is a crucial regulator of systemic iron homeostasis, controlling both iron absorption by enterocytes and its release by macrophages. Mutations in Hepcidin gene (HAMP) result in the development of a juvenile type of HH. Also, it has been hypothesized that, in certain conditions, some HAMP polymorphisms can modulate iron status. As example, c.-582A>G polymorphism in HAMP promoter can increase serum ferritin levels in beta-thalassemia major patients, but not in normal individuals. HAMP promoter polymorphisms were analysed by DNA sequencing in 266 individuals with ferritin levels higher than 400ng/mL: i) 191 individuals homozygous or heterozygous for the H63D mutation (group 1) and ii) 75 individuals carrying one or more C282Y alleles (HH/CY, HH/YY or HD/CY) (group 2). Also, luminescence assays were performed in Huh-7 cells in order to assess whether the HAMP promoter polymorphisms are changing the hepcidin expression in response to external stimulus. The results revealed that c.-582A>G is in linkage with c.-1010C>T polymorphism. These polymorphisms were found in a significant higher frequency in group 1 (31.2% of allele G and T, respectively) than in the general population (16.4%; p<0.001). Furthermore, they were found at a slight higher, but not significant frequency at group 2 (21.3%), comparing with general population (p=0.186). Functional in vitro studies, using stimulus as holo-transferrin, ferric citrate, IL-6, hypoxia or GDF15, revealed no differences in the activity of the HAMP promoter in the presence or absence of these polymorphisms. We conclude that c.-1010C>T and c.-582A>G polymorphisms seem to modulate iron overload development in individuals carrying the H63D mutation. However, the mechanism subjacent to this observation remains elusive.
Arbitragem científica: yes
URI: http://hdl.handle.net/10400.18/401
Appears in Collections:DGH - Posters/abstracts em congressos nacionais

Files in This Item:

File Description SizeFormat
Poster SPGH 2011_Bruno Silva.pdf654,45 kBAdobe PDFView/Open

Please give feedback about this item
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