TY - JOUR
T1 - Association of HFE and TMPRSS6 genetic variants with iron and erythrocyte parameters is only in part dependent on serum hepcidin concentrations
AU - Traglia, Michela
AU - Girelli, Domenico
AU - Biino, Ginevra
AU - Campostrini, Natascia
AU - Corbella, Michela
AU - Sala, Cinzia
AU - Masciullo, Corrado
AU - Viganò, Fiammetta
AU - Buetti, Iwan
AU - Pistis, Giorgio
AU - Cocca, Massimiliano
AU - Camaschella, Clara
AU - Toniolo, Daniela
PY - 2011/9
Y1 - 2011/9
N2 - Background: Hepcidin is the main regulator of iron homeostasis: inappropriate production of hepcidin results in iron overload or iron deficiency and anaemia. Aims: To study variation of serum hepcidin concentration in a normal population. Results: Hepcidin showed age and sex dependent variations that correlated with ferritin but not with serum iron and transferrin saturation. The size of the study population was underpowered to find genome wide significant associations with hepcidin concentrations but it allowed to show that association with serum iron, transferrin saturation and erythrocyte traits of common DNA variants in HFE (rs1800562) and TMPRSS6 (rs855791) genes is not exclusively dependent on hepcidin values. When multiple interactions between environmental factors, the iron parameters and hepcidin were taken into account, the HFE variant, and to lesser extent the TMPRSS6 variant, were associated with ferritin and with hepcidin normalised to ferritin (the hepcidin/ferritin ratio). Conclusions: The results suggest a mutual control of serum hepcidin and ferritin concentrations, a mechanism relevant to the pathophysiology of HFE haemochromatosis, and demonstrate that the HFE rs1800562 C282Y variant exerts a direct pleiotropic effect on the iron parameters, in part independent of hepcidin.
AB - Background: Hepcidin is the main regulator of iron homeostasis: inappropriate production of hepcidin results in iron overload or iron deficiency and anaemia. Aims: To study variation of serum hepcidin concentration in a normal population. Results: Hepcidin showed age and sex dependent variations that correlated with ferritin but not with serum iron and transferrin saturation. The size of the study population was underpowered to find genome wide significant associations with hepcidin concentrations but it allowed to show that association with serum iron, transferrin saturation and erythrocyte traits of common DNA variants in HFE (rs1800562) and TMPRSS6 (rs855791) genes is not exclusively dependent on hepcidin values. When multiple interactions between environmental factors, the iron parameters and hepcidin were taken into account, the HFE variant, and to lesser extent the TMPRSS6 variant, were associated with ferritin and with hepcidin normalised to ferritin (the hepcidin/ferritin ratio). Conclusions: The results suggest a mutual control of serum hepcidin and ferritin concentrations, a mechanism relevant to the pathophysiology of HFE haemochromatosis, and demonstrate that the HFE rs1800562 C282Y variant exerts a direct pleiotropic effect on the iron parameters, in part independent of hepcidin.
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U2 - 10.1136/jmedgenet-2011-100061
DO - 10.1136/jmedgenet-2011-100061
M3 - Article
C2 - 21785125
AN - SCOPUS:80052587883
VL - 48
SP - 629
EP - 634
JO - Journal of Medical Genetics
JF - Journal of Medical Genetics
SN - 0022-2593
IS - 9
ER -