




Item type: | Article | ||||
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Journal or Publication Title: | Human Molecular Genetics | ||||
Publisher: | OXFORD UNIV PRESS | ||||
Place of Publication: | OXFORD | ||||
Volume: | 20 | ||||
Number of Issue or Book Chapter: | 6 | ||||
Page Range: | pp. 1232-1240 | ||||
Date: | 2010 | ||||
Institutions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin | ||||
Identification Number: |
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Keywords: | TRANSFERRIN RECEPTOR 2; PROTEASE MATRIPTASE-2 TMPRSS6; GENOME-WIDE ASSOCIATION; HEREDITARY HEMOCHROMATOSIS; SERINE-PROTEASE; ISOLATED POPULATION; FERRITIN LEVELS; HEPCIDIN; ANEMIA; HOMEOSTASIS; | ||||
Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||
Status: | Published | ||||
Refereed: | Yes, this version has been refereed | ||||
Created at the University of Regensburg: | Yes | ||||
Item ID: | 65110 |
Abstract
The genetic determinants of variation in iron status are actively sought, but remain incompletely understood. Meta-analysis of two genome-wide association (GWA) studies and replication in three independent cohorts was performed to identify genetic loci associated in the general population with serum levels of iron and markers of iron status, including transferrin, ferritin, soluble transferrin ...

Abstract
The genetic determinants of variation in iron status are actively sought, but remain incompletely understood. Meta-analysis of two genome-wide association (GWA) studies and replication in three independent cohorts was performed to identify genetic loci associated in the general population with serum levels of iron and markers of iron status, including transferrin, ferritin, soluble transferrin receptor (sTfR) and sTfR-ferritin index. We identified and replicated a novel association of a common variant in the type-2 transferrin receptor (TFR2) gene with iron levels, with effect sizes highly consistent across samples. In addition, we identified and replicated an association between the HFE locus and ferritin and confirmed previously reported associations with the TF, TMPRSS6 and HFE genes. The five replicated variants were tested for association with expression levels of the corresponding genes in a publicly available data set of human liver samples, and nominally statistically significant expression differences by genotype were observed for all genes, although only rs3811647 in the TF gene survived the Bonferroni correction for multiple testing. In addition, we measured for the first time the effects of the common variant in TMPRSS6, rs4820268, on hepcidin mRNA in peripheral blood (n = 83 individuals) and on hepcidin levels in urine (n = 529) and observed an association in the same direction, though only borderline significant. These functional findings require confirmation in further studies with larger sample sizes, but they suggest that common variants in TMPRSS6 could modify the hepcidin-iron feedback loop in clinically unaffected individuals, thus making them more susceptible to imbalances of iron homeostasis.
Metadata last modified: 19 Dec 2024 11:13