RT Journal Article
T1 Genetic study of the hepcidin gene (HAMP) promoter and functional analysis of the c.-582A > G variant
A1 Parajes Castro, Silvia
A1 González Quintela, Arturo
A1 Campos Franco, Joaquín
A1 Quinteiro García, Celsa
A1 Domínguez Puente, Fernando Ignacio
A1 Loidi, Lourdes
K1 Iron Overload
K1 Serum Iron
K1 Serum Ferritin Level
K1 Transferrin Saturation
K1 Serum Transferrin
AB BackgroundHepcidin 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 (HAMP) promoter, to asses the associations between the variants found and iron status parameters, and to functionally study the role on HAMP expression of the most frequent variant.ResultsThe sequencing of HAMP 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.The c.-582G HAMP 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).ConclusionsThe c.-582A > G HAMP promoter variant is not associated with serum iron, transferrin or ferritin levels in the healthy population. The in vitro 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 in vivo 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
PB BMC
SN 1471-2156
YR 2010
FD 2010
LK http://hdl.handle.net/10347/22883
UL http://hdl.handle.net/10347/22883
LA eng
NO Parajes, S., González-Quintela, A., Campos, J. et al. Genetic study of the hepcidin gene (HAMP) promoter and functional analysis of the c.-582A > G variant. BMC Genet 11, 110 (2010). https://doi.org/10.1186/1471-2156-11-110
NO This work was supported by a grant from the Fondo de Investigaciones Sanitarias del Instituto de Salud Carlos III (PI052249 to LL) and Xunta de Galicia (PGIDIT06PXIC9101136PN)
DS Minerva
RD 28 abr 2026