Abstract
The iron hormone hepcidin is inhibited by matriptase-2 (MT2), a liver serine protease encoded by the TMPRSS6 gene. Cleaving the bone morphogenetic protein (BMP) coreceptor hemojuvelin (HJV), MT2 impairs the BMP/son of mothers against decapentaplegic homologs (SMAD) signaling pathway, down-regulates hepcidin, and facilitates iron absorption.TMPRSS6 inactivation causes iron-deficiency anemia refractory to iron administration both in humans and mice. Genome-wide association studies have shown that the SNP rs855791, which causes the MT2 V736A amino acid substitution, is associated with variations of serum iron, transferrin saturation, hemoglobin, and erythrocyte traits. In the present study, we show that, in vitro, MT2 736 A inhibits hepcidin more efficiently than 736 V. Moreover, in a genotyped population, after exclusion of samples with iron deficiency and inflammation, hepcidin, hepcidin/transferrin saturation, and hepcidin/ferritin ratios were significantly lower and iron parameters were consistently higher in homozygotes 736 A than in 736 V. Our results indicate that rs855791 is a TMPRSS6 functional variant and strengthen the idea that even a partial inability to modulate hepcidin influences iron parameters and, indirectly, erythropoiesis.
| Original language | English |
|---|---|
| Pages (from-to) | 4459-4462 |
| Number of pages | 4 |
| Journal | Blood |
| Volume | 118 |
| Issue number | 16 |
| DOIs | |
| Publication status | Published - Oct 20 2011 |
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ASJC Scopus subject areas
- Hematology
- Biochemistry
- Cell Biology
- Immunology
Cite this
TMPRSS6 rs855791 modulates hepcidin transcription in vitro and serum hepcidin levels in normal individuals. / Nai, Antonella; Pagani, Alessia; Silvestri, Laura; Campostrini, Natascia; Corbella, Michela; Girelli, Domenico; Traglia, Michela; Toniolo, Daniela; Camaschella, Clara.
In: Blood, Vol. 118, No. 16, 20.10.2011, p. 4459-4462.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - TMPRSS6 rs855791 modulates hepcidin transcription in vitro and serum hepcidin levels in normal individuals
AU - Nai, Antonella
AU - Pagani, Alessia
AU - Silvestri, Laura
AU - Campostrini, Natascia
AU - Corbella, Michela
AU - Girelli, Domenico
AU - Traglia, Michela
AU - Toniolo, Daniela
AU - Camaschella, Clara
PY - 2011/10/20
Y1 - 2011/10/20
N2 - The iron hormone hepcidin is inhibited by matriptase-2 (MT2), a liver serine protease encoded by the TMPRSS6 gene. Cleaving the bone morphogenetic protein (BMP) coreceptor hemojuvelin (HJV), MT2 impairs the BMP/son of mothers against decapentaplegic homologs (SMAD) signaling pathway, down-regulates hepcidin, and facilitates iron absorption.TMPRSS6 inactivation causes iron-deficiency anemia refractory to iron administration both in humans and mice. Genome-wide association studies have shown that the SNP rs855791, which causes the MT2 V736A amino acid substitution, is associated with variations of serum iron, transferrin saturation, hemoglobin, and erythrocyte traits. In the present study, we show that, in vitro, MT2 736 A inhibits hepcidin more efficiently than 736 V. Moreover, in a genotyped population, after exclusion of samples with iron deficiency and inflammation, hepcidin, hepcidin/transferrin saturation, and hepcidin/ferritin ratios were significantly lower and iron parameters were consistently higher in homozygotes 736 A than in 736 V. Our results indicate that rs855791 is a TMPRSS6 functional variant and strengthen the idea that even a partial inability to modulate hepcidin influences iron parameters and, indirectly, erythropoiesis.
AB - The iron hormone hepcidin is inhibited by matriptase-2 (MT2), a liver serine protease encoded by the TMPRSS6 gene. Cleaving the bone morphogenetic protein (BMP) coreceptor hemojuvelin (HJV), MT2 impairs the BMP/son of mothers against decapentaplegic homologs (SMAD) signaling pathway, down-regulates hepcidin, and facilitates iron absorption.TMPRSS6 inactivation causes iron-deficiency anemia refractory to iron administration both in humans and mice. Genome-wide association studies have shown that the SNP rs855791, which causes the MT2 V736A amino acid substitution, is associated with variations of serum iron, transferrin saturation, hemoglobin, and erythrocyte traits. In the present study, we show that, in vitro, MT2 736 A inhibits hepcidin more efficiently than 736 V. Moreover, in a genotyped population, after exclusion of samples with iron deficiency and inflammation, hepcidin, hepcidin/transferrin saturation, and hepcidin/ferritin ratios were significantly lower and iron parameters were consistently higher in homozygotes 736 A than in 736 V. Our results indicate that rs855791 is a TMPRSS6 functional variant and strengthen the idea that even a partial inability to modulate hepcidin influences iron parameters and, indirectly, erythropoiesis.
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U2 - 10.1182/blood-2011-06-364034
DO - 10.1182/blood-2011-06-364034
M3 - Article
VL - 118
SP - 4459
EP - 4462
JO - Blood
JF - Blood
SN - 0006-4971
IS - 16
ER -