The TMPRSS6 variant (SNP rs855791) affects iron metabolism and oral iron absorption - a stable iron isotope study in Taiwanese women.
- Buerkli S Laboratory of Human Nutrition, Institute of Food Nutrition and Health, Department of Health Science and Technology, Swiss Federal Institute of Technology (ETH Zurich), Zurich, Switzerland.
- Pei SN Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan; Department of Hematology Oncology, E-Da Cancer Hospital, Taiwan; College of Medicine, I-Shou University, Kaohsiung, Taiwan.
- Hsiao SC Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Taiwan.
- Lee CT Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
- Zeder C Laboratory of Human Nutrition, Institute of Food Nutrition and Health, Department of Health Science and Technology, Swiss Federal Institute of Technology (ETH Zurich), Zurich, Switzerland.
- Zimmermann MB Laboratory of Human Nutrition, Institute of Food Nutrition and Health, Department of Health Science and Technology, Swiss Federal Institute of Technology (ETH Zurich), Zurich, Switzerland.
- Moretti D Laboratory of Human Nutrition, Institute of Food Nutrition and Health, Department of Health Science and Technology, Swiss Federal Institute of Technology (ETH Zurich), Zurich, Switzerland; Current address: Swiss Distance University of Applied Sciences, Department of Health, Regensdorf/Zurich, Switzerland. diego.moretti@alumni.ethz.ch.
- 2020-10-15
Published in:
- Haematologica. - 2020
English
Genome wide studies have associated TMPRSS6 rs855791 (2321 C>T) with iron status
and hepcidin. It is unclear whether this polymorphism affects iron absorption. In
nonanemic Taiwanese women (n=79, 44 TT variant, 35 CC variant), we administered
standardized rice-based test meals containing 4 mg of labeled 57Fe or 58Fe as FeSO4 on
alternate days. Fractional iron absorption was measured by erythrocyte incorporation of
the tracers 14 days after administration. Compared to the CC variant, in the TT variant
serum iron and transferrin saturation were lower (P=0.001; P<0.001, respectively) and
serum hepcidin/transferrin saturation and serum hepcidin/serum iron ratios were higher
(P=0.042; P=0.088, respectively). Serum hepcidin did not differ between groups
(P=0.862). Geometric mean (95% CI) fractional iron absorption, corrected to a serum
ferritin of 15 μg/L, was 26.6% (24.0, 29.5) in the CC variant and 18.5% (16.2, 21.1) in the
TT variant (P=0.002). Overall, predictors of iron absorption were: serum ferritin
(P<0.001); genetic variant (P=0.032); and hepcidin (P<0.001). In the models by variant,
in the CC variant the model explained 67-71% of variability in absorption and serum
ferritin was the only significant predictor (P<0.001); in the TT variant, the model
explained only 35-43% of variability, and hemoglobin (P=0.032), soluble transferrin
receptor (P=0.004) and hepcidin (P<0.001) were significant predictors. Women with the
TMPRSS6 rs855791 (2321 C>T) polymorphism show altered iron homeostasis which
affects oral iron absorption and may increase their risk for iron deficiency. The trial was
registered at www.clinicaltrials.gov as NCT03317873, and funded by the Kaohsiung
Chang-Gung Memorial Hospital, Kaohsiung, Taiwan, (grant CMRPG8F0721) and ETH
Zurich, Switzerland.
and hepcidin. It is unclear whether this polymorphism affects iron absorption. In
nonanemic Taiwanese women (n=79, 44 TT variant, 35 CC variant), we administered
standardized rice-based test meals containing 4 mg of labeled 57Fe or 58Fe as FeSO4 on
alternate days. Fractional iron absorption was measured by erythrocyte incorporation of
the tracers 14 days after administration. Compared to the CC variant, in the TT variant
serum iron and transferrin saturation were lower (P=0.001; P<0.001, respectively) and
serum hepcidin/transferrin saturation and serum hepcidin/serum iron ratios were higher
(P=0.042; P=0.088, respectively). Serum hepcidin did not differ between groups
(P=0.862). Geometric mean (95% CI) fractional iron absorption, corrected to a serum
ferritin of 15 μg/L, was 26.6% (24.0, 29.5) in the CC variant and 18.5% (16.2, 21.1) in the
TT variant (P=0.002). Overall, predictors of iron absorption were: serum ferritin
(P<0.001); genetic variant (P=0.032); and hepcidin (P<0.001). In the models by variant,
in the CC variant the model explained 67-71% of variability in absorption and serum
ferritin was the only significant predictor (P<0.001); in the TT variant, the model
explained only 35-43% of variability, and hemoglobin (P=0.032), soluble transferrin
receptor (P=0.004) and hepcidin (P<0.001) were significant predictors. Women with the
TMPRSS6 rs855791 (2321 C>T) polymorphism show altered iron homeostasis which
affects oral iron absorption and may increase their risk for iron deficiency. The trial was
registered at www.clinicaltrials.gov as NCT03317873, and funded by the Kaohsiung
Chang-Gung Memorial Hospital, Kaohsiung, Taiwan, (grant CMRPG8F0721) and ETH
Zurich, Switzerland.
- Language
-
- English
- Open access status
- gold
- Identifiers
-
- DOI 10.3324/haematol.2020.264556
- PMID 33054130
- Persistent URL
- https://sonar.ch/global/documents/238803
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