title: Novel association to the proprotein convertase PCSK7 gene locus revealed by analysing soluble transferrin receptor (sTfR) levels.
abstract: The level of body iron storage and the erythropoietic need for iron are indicated by the serum levels of ferritin and soluble transferrin receptor (sTfR), respectively. A meta-analysis of five genome-wide association studies on sTfR and ferritin revealed novel association to the PCSK7 and TMPRSS6 loci for sTfR and the HFE locus for both parameters. The PCSK7 association was the most significant (rs236918, P = 1.1 × 10E-27) suggesting that proprotein convertase 7, the gene product of PCSK7, may be involved in sTfR generation and/or iron homeostasis. Conditioning the sTfR analyses on transferrin saturation abolished the HFE signal and substantially diminished the TMPRSS6 signal while the PCSK7 association was unaffected, suggesting that the former may be mediated by transferrin saturation whereas the PCSK7-associated effect on sTfR generation appears to be more direct.
authors.affiliation: Institute of Human Genetics, MRI, Technische Universität München, Munich, Germany. oexle@humangenetik.med.tum.de
authors.forename: Konrad
authors.initials: K
authors.lastname: Oexle
authors.forename: Janina S
authors.initials: JS
authors.lastname: Ried
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Hicks
authors.forename: Toshiko
authors.initials: T
authors.lastname: Tanaka
authors.forename: Caroline
authors.initials: C
authors.lastname: Hayward
authors.forename: Mathias
authors.initials: M
authors.lastname: Bruegel
authors.forename: Martin
authors.initials: M
authors.lastname: Gögele
authors.forename: Peter
authors.initials: P
authors.lastname: Lichtner
authors.forename: Bertram
authors.initials: B
authors.lastname: Müller-Myhsok
authors.forename: Angela
authors.initials: A
authors.lastname: Döring
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Christine
authors.initials: C
authors.lastname: Schwienbacher
authors.forename: Cosetta
authors.initials: C
authors.lastname: Minelli
authors.forename: Irene
authors.initials: I
authors.lastname: Pichler
authors.forename: G Martin
authors.initials: GM
authors.lastname: Fiedler
authors.forename: Joachim
authors.initials: J
authors.lastname: Thiery
authors.forename: Igor
authors.initials: I
authors.lastname: Rudan
authors.forename: Alan F
authors.initials: AF
authors.lastname: Wright
authors.forename: Harry
authors.initials: H
authors.lastname: Campbell
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: Stefania
authors.initials: S
authors.lastname: Bandinelli
authors.forename: Peter P
authors.initials: PP
authors.lastname: Pramstaller
authors.forename: H-Erich
authors.initials: HE
authors.lastname: Wichmann
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.forename: Juliane
authors.initials: J
authors.lastname: Winkelmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Meitinger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D007501:Iron / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011990:Receptors, Transferrin / Q000235:genetics* / Q000378:metabolism; D013381:Subtilisins / Q000235:genetics*; D055815:Young Adult
chemical_list: D011990:Receptors, Transferrin; D007501:Iron; C099101:PCSK7 protein, human; D013381:Subtilisins