Identification of a common variant in the TFR2 gene implicated in the physiological regulation of serum iron levels.

Détails

ID Serval
serval:BIB_2EF268CFEB5E
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Identification of a common variant in the TFR2 gene implicated in the physiological regulation of serum iron levels.
Périodique
Human molecular genetics
Auteur(s)
Pichler I., Minelli C., Sanna S., Tanaka T., Schwienbacher C., Naitza S., Porcu E., Pattaro C., Busonero F., Zanon A., Maschio A., Melville S.A., Grazia Piras M., Longo D.L., Guralnik J., Hernandez D., Bandinelli S., Aigner E., Murphy A.T., Wroblewski V., Marroni F., Theurl I., Gnewuch C., Schadt E., Mitterer M., Schlessinger D., Ferrucci L., Witcher D.R., Hicks A.A., Weiss G., Uda M., Pramstaller P.P.
ISSN
1460-2083 (Electronic)
ISSN-L
0964-6906
Statut éditorial
Publié
Date de publication
15/03/2011
Peer-reviewed
Oui
Volume
20
Numéro
6
Pages
1232-1240
Langue
anglais
Notes
Publication types: Journal Article ; Meta-Analysis ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
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.
Mots-clé
Adult, Aged, Aged, 80 and over, Cross-Sectional Studies, Female, Genetic Variation, Humans, Iron/blood, Male, Middle Aged, Polymorphism, Single Nucleotide, Receptors, Transferrin/genetics, Receptors, Transferrin/metabolism, Young Adult
Pubmed
Web of science
Open Access
Oui
Création de la notice
18/01/2021 22:51
Dernière modification de la notice
19/01/2021 7:26
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