Genetic study of the hepcidin gene (<it>HAMP</it>) promoter and functional analysis of the c.-582A > G variant
<p>Abstract</p> <p>Background</p> <p>Hepcidin acts as the main regulator of iron homeostasis through regulation of intestinal absorption and macrophage release. Hepcidin deficiency causes iron overload whereas its overproduction is associated with anaemia of chronic dis...
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| Format: | Article |
| Language: | English |
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BMC
2010-12-01
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| Series: | BMC Genetics |
| Online Access: | http://www.biomedcentral.com/1471-2156/11/110 |
| _version_ | 1828544394166272000 |
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| author | Domínguez Fernando Quinteiro Celsa Campos Joaquín González-Quintela Arturo Parajes Silvia Loidi Lourdes |
| author_facet | Domínguez Fernando Quinteiro Celsa Campos Joaquín González-Quintela Arturo Parajes Silvia Loidi Lourdes |
| author_sort | Domínguez Fernando |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Hepcidin acts as the main regulator of iron homeostasis through regulation of intestinal absorption and macrophage release. Hepcidin deficiency causes iron overload whereas its overproduction is associated with anaemia of chronic diseases. The aims of the study were: to identify genetic variants in the hepcidin gene (<it>HAMP</it>) promoter, to asses the associations between the variants found and iron status parameters, and to functionally study the role on <it>HAMP </it>expression of the most frequent variant.</p> <p>Results</p> <p>The sequencing of <it>HAMP </it>promoter from 103 healthy individuals revealed two genetic variants: The c.-153C > T with a frequency of 0.014 for allele T, which is known to reduce hepcidin expression and the c.-582A > G with a 0.218 frequency for allele G. In an additional group of 224 individuals, the c.-582A > G variant genotype showed no association with serum iron, transferrin or ferritin levels.</p> <p>The c.-582G <it>HAMP </it>promoter variant decreased the transcriptional activity by 20% compared to c.-582A variant in cells from the human hepatoma cell line HepG2 when cotransfected with luciferase reporter constructs and plasmid expressing upstream stimulatory factor 1 (USF1) and by 12-14% when cotransfected with plasmid expressing upstream stimulatory factor 2 (USF2).</p> <p>Conclusions</p> <p>The c.-582A > G <it>HAMP </it>promoter variant is not associated with serum iron, transferrin or ferritin levels in the healthy population. The <it>in vitro </it>effect of the c.-582A > G variant resulted in a small reduction of the gene transactivation by allele G compared to allele A. Therefore the effect of the variant on the hepcidin levels <it>in vivo </it>would be likely negligible. Finally, the c.-153C > T variant showed a frequency high enough to be considered when a genetic analysis is done in iron overload patients.</p> |
| first_indexed | 2024-12-12T02:29:54Z |
| format | Article |
| id | doaj.art-8f3a093fdbb6417fb8daba29a918f738 |
| institution | Directory Open Access Journal |
| issn | 1471-2156 |
| language | English |
| last_indexed | 2024-12-12T02:29:54Z |
| publishDate | 2010-12-01 |
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| series | BMC Genetics |
| spelling | doaj.art-8f3a093fdbb6417fb8daba29a918f7382022-12-22T00:41:27ZengBMCBMC Genetics1471-21562010-12-0111111010.1186/1471-2156-11-110Genetic study of the hepcidin gene (<it>HAMP</it>) promoter and functional analysis of the c.-582A > G variantDomínguez FernandoQuinteiro CelsaCampos JoaquínGonzález-Quintela ArturoParajes SilviaLoidi Lourdes<p>Abstract</p> <p>Background</p> <p>Hepcidin acts as the main regulator of iron homeostasis through regulation of intestinal absorption and macrophage release. Hepcidin deficiency causes iron overload whereas its overproduction is associated with anaemia of chronic diseases. The aims of the study were: to identify genetic variants in the hepcidin gene (<it>HAMP</it>) promoter, to asses the associations between the variants found and iron status parameters, and to functionally study the role on <it>HAMP </it>expression of the most frequent variant.</p> <p>Results</p> <p>The sequencing of <it>HAMP </it>promoter from 103 healthy individuals revealed two genetic variants: The c.-153C > T with a frequency of 0.014 for allele T, which is known to reduce hepcidin expression and the c.-582A > G with a 0.218 frequency for allele G. In an additional group of 224 individuals, the c.-582A > G variant genotype showed no association with serum iron, transferrin or ferritin levels.</p> <p>The c.-582G <it>HAMP </it>promoter variant decreased the transcriptional activity by 20% compared to c.-582A variant in cells from the human hepatoma cell line HepG2 when cotransfected with luciferase reporter constructs and plasmid expressing upstream stimulatory factor 1 (USF1) and by 12-14% when cotransfected with plasmid expressing upstream stimulatory factor 2 (USF2).</p> <p>Conclusions</p> <p>The c.-582A > G <it>HAMP </it>promoter variant is not associated with serum iron, transferrin or ferritin levels in the healthy population. The <it>in vitro </it>effect of the c.-582A > G variant resulted in a small reduction of the gene transactivation by allele G compared to allele A. Therefore the effect of the variant on the hepcidin levels <it>in vivo </it>would be likely negligible. Finally, the c.-153C > T variant showed a frequency high enough to be considered when a genetic analysis is done in iron overload patients.</p>http://www.biomedcentral.com/1471-2156/11/110 |
| spellingShingle | Domínguez Fernando Quinteiro Celsa Campos Joaquín González-Quintela Arturo Parajes Silvia Loidi Lourdes Genetic study of the hepcidin gene (<it>HAMP</it>) promoter and functional analysis of the c.-582A > G variant BMC Genetics |
| title | Genetic study of the hepcidin gene (<it>HAMP</it>) promoter and functional analysis of the c.-582A > G variant |
| title_full | Genetic study of the hepcidin gene (<it>HAMP</it>) promoter and functional analysis of the c.-582A > G variant |
| title_fullStr | Genetic study of the hepcidin gene (<it>HAMP</it>) promoter and functional analysis of the c.-582A > G variant |
| title_full_unstemmed | Genetic study of the hepcidin gene (<it>HAMP</it>) promoter and functional analysis of the c.-582A > G variant |
| title_short | Genetic study of the hepcidin gene (<it>HAMP</it>) promoter and functional analysis of the c.-582A > G variant |
| title_sort | genetic study of the hepcidin gene it hamp it promoter and functional analysis of the c 582a g variant |
| url | http://www.biomedcentral.com/1471-2156/11/110 |
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