Pichler, Irene and Minelli, Cosetta and Sanna, Serena and Tanaka, Toshiko and Schwienbacher, Christine and Naitza, Silvia and Porcu, Eleonora and Pattaro, Cristian and Busonero, Fabio and Zanon, Alessandra and Maschio, Andrea and Melville, Scott A. and Piras, Maria Grazia and Longo, Dan L. and Guralnik, Jack and Hernandez, Dena and Bandinelli, Stefania and Aigner, Elmar and Murphy, Anthony T. and Wroblewski, Victor and Marroni, Fabio and Theurl, Igor and Gnewuch, Carsten and Schadt, Eric and Mitterer, Manfred and Schlessinger, David and Ferrucci, Luigi and Witcher, Derrick R. and Hicks, Andrew A. and Weiss, Guenter and Uda, Manuela and Pramstaller, Peter P. (2011) Identification of a common variant in the TFR2 gene implicated in the physiological regulation of serum iron levels. HUMAN MOLECULAR GENETICS, 20 (6). pp. 1232-1240. ISSN 0964-6906,
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TRANSFERRIN RECEPTOR 2; PROTEASE MATRIPTASE-2 TMPRSS6; GENOME-WIDE ASSOCIATION; HEREDITARY HEMOCHROMATOSIS; SERINE-PROTEASE; ISOLATED POPULATION; FERRITIN LEVELS; HEPCIDIN; ANEMIA; HOMEOSTASIS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Jun 2020 05:35 |
| Last Modified: | 24 Jun 2020 05:35 |
| URI: | https://pred.uni-regensburg.de/id/eprint/21114 |
Actions (login required)
 |
View Item |
