{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T10:29:29Z","timestamp":1794047369241,"version":"4.8.0"},"reference-count":40,"publisher":"Ferrata Storti Foundation (Haematologica)","issue":"11","license":[{"start":{"date-parts":[[2020,10,5]],"date-time":"2020-10-05T00:00:00Z","timestamp":1601856000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["haematol"],"abstract":"<jats:p>Genome wide studies have associated TMPRSS6 rs855791 (2321 C&gt;T) with iron status and hepcidin. It is unclear whether this polymorphism affects iron absorption. We administered standardized ricebased test meals containing 4 mg of labeled 57Fe or 58Fe as FeSO4 on alternate days in non-anemic Taiwanese women (n=79, 44 TT variant, 35 CC variant). Fractional iron absorption was measured by erythrocyte incorporation of the tracers 14 days after administration. Compared to the CC variant, iron and transferrin saturation were lower (P=0.001; P&lt;0.001, respectively) and serum hepcidin\/transferrin saturation and serum hepcidin\/serum iron ratios were higher (P=0.042; P=0.088, respectively) in the TT variant. Serum hepcidin did not differ between the groups (P=0.862). Geometric mean (95% Confidence Interval [CI]) fractional iron absorption, corrected to a serum ferritin of 15 \u03bcg\/L, was 26.6% (95% CI: 24.0-29.5) in the CC variant and 18.5% (95% CI: 16.2-21.1) in the TT variant (P=0.002). Overall, predictors of iron absorption were: serum ferritin (P&lt;0.001); genetic variant (P=0.032); and hepcidin (P&lt;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&lt;0.001); while 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&lt;0.001) were significant predictors. Women with the TMPRSS6 rs855791 (2321 C&gt;T) polymorphism show altered iron homeostasis which affects oral iron absorption and may increase their risk for iron deficiency. The trial was registered as clinicaltrials gov. Identifier: NCT03317873, and funded by the Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan, (grant CMRPG8F0721) and ETH Zurich, Switzerland.<\/jats:p>","DOI":"10.3324\/haematol.2020.264556","type":"journal-article","created":{"date-parts":[[2020,10,5]],"date-time":"2020-10-05T14:42:17Z","timestamp":1601908937000},"page":"2897-2905","source":"Crossref","is-referenced-by-count":19,"title":["The &lt;i&gt;TMPRSS6&lt;\/i&gt; variant (SNP rs855791) affects iron metabolism and oral iron absorption \u2013 a stable iron isotope study in Taiwanese women"],"prefix":"10.3324","volume":"106","author":[{"given":"Simone","family":"Buerkli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Nan","family":"Pei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Chen","family":"Hsiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Te","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Zeder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B.","family":"Zimmermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Moretti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1856","published-online":{"date-parts":[[2020,10,5]]},"reference":[{"key":"31023","doi-asserted-by":"crossref","unstructured":"Zumerle S, Mathieu JR, Delga S. 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Mutat Res. 2019; 779:58-67.","DOI":"10.1016\/j.mrrev.2019.01.002"},{"key":"31034","doi-asserted-by":"crossref","unstructured":"Benyamin B, Ferreira MA, Willemsen G. Common variants in TMPRSS6 are associated with iron status and erythrocyte volume. Nat Genet. 2009; 41(11):1173-1175.","DOI":"10.1038\/ng.456"},{"key":"31035","doi-asserted-by":"crossref","unstructured":"Kamatani Y, Matsuda K, Okada Y. Genome-wide association study of hematological and biochemical traits in a Japanese population. Nat Genet. 2010; 42(3):210-215.","DOI":"10.1038\/ng.531"},{"key":"31036","doi-asserted-by":"crossref","unstructured":"Sorensen E, Rigas AS, Thorner LW. Genetic factors influencing ferritin levels in 14,126 blood donors: results from the Danish Blood Donor Study. Transfusion. 2015; 56(3):622-627.","DOI":"10.1111\/trf.13397"},{"key":"31037","doi-asserted-by":"crossref","unstructured":"Sorensen E, Rigas AS, Didriksen M. Genetic factors influencing hemoglobin levels in 15,567 blood donors: results from the Danish Blood Donor Study. Transfusion. 2019; 59(1):226-231.","DOI":"10.1111\/trf.15075"},{"key":"31038","doi-asserted-by":"crossref","unstructured":"Gan W, Guan Y, Wu Q. Association of TMPRSS6 polymorphisms with ferritin, hemoglobin, and type 2 diabetes risk in a Chinese Han population. Am J Clin Nutr. 2012; 95(3):626-632.","DOI":"10.3945\/ajcn.111.025684"},{"key":"31039","doi-asserted-by":"crossref","unstructured":"An P, Wu Q, Wang H. TMPRSS6, but not TF, TFR2 or BMP2 variants are associated with increased risk of iron-deficiency anemia. Hum Mol Genet. 2012; 21(9):2124-2131.","DOI":"10.1093\/hmg\/dds028"},{"key":"31040","doi-asserted-by":"crossref","unstructured":"Nai A, Pagani A, Silvestri L. TMPRSS6 rs855791 modulates hepcidin transcription in vitro and serum hepcidin levels in normal individuals. 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The opposing effects of acute inflammation and iron deficiency anemia on serum hepcidin and iron absorption in young women. Haematologica. 2019; 104(6):1143-1149.","DOI":"10.3324\/haematol.2018.208645"},{"key":"31059","doi-asserted-by":"crossref","unstructured":"Moretti D, Goede JS, Zeder C. Oral iron supplements increase hepcidin and decrease iron absorption from daily or twice-daily doses in iron-depleted young women. Blood. 2015; 126(17):1981-1989.","DOI":"10.1182\/blood-2015-05-642223"},{"key":"31060","doi-asserted-by":"crossref","unstructured":"Mah YH, Kao JH, Liu CJ. Prevalence and clinical implications of HFE gene mutations (C282Y and H63D) in patients with chronic hepatitis B and C in Taiwan. Liver Int. 2005; 25(2):214-219.","DOI":"10.1111\/j.1478-3231.2005.01055.x"},{"key":"31061","doi-asserted-by":"crossref","unstructured":"Bardou-Jacquet E, de Tayrac M, Mosser J, Deugnier Y. GNPAT variant associated with severe iron overload in HFE hemochromatosis. 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