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Title: Indications for a genetic association of a VCP polymorphism with the pathogenesis of sporadic Paget's disease of bone, but not for TNFSF11 (RANKL) and IL-6 polymorphisms
Authors: Chung, Pui Yan Jenny
Beyens, Greet
de Freitas, Fenna
Boonen, Steven
Vanhoenacker, Filip
Verbruggen, Leon
Van Offel, Jan
Goemaere, Stefan
Zmierczak, Hans-Georg
Westhovens, Rene
Devogelaer, Jean-Pierre
Van Hul, Wim
Issue Date: 2011
Citation: MOLECULAR GENETICS AND METABOLISM, 103(3). p. 287-292
Abstract: Paget's disease of bone (PDB) is, after osteoporosis, the second most common metabolic bone disorder in the elderly Caucasian population. Mutations in the sequestosome 1 gene (SQSTM1) are responsible for the etiology of PDB in a subset of patients, but the disease pathogenesis in the remaining PDB patients is still unknown. Therefore association studies investigating the relationship between genetic polymorphisms and sporadic PDB have been performed in order to find the susceptibility polymorphisms. In this paper, we sought to determine whether polymorphisms in 3 functional candidate genes play a role in the development of sporadic PDB: TNFSF11 (receptor activator of nuclear factor kappa B ligand, RANKL), VCP (valosin-containing protein) and IL-6 (interleukin 6). Analyzing 9 tag SNPs and 2 multi-marker tests (MMTs) in TNFSF11, 3 tag SNPs and 1 MMT in VCP and 8 tag SNPs in IL-6 in a population of 196 Belgian patients with sporadic PDB and 212 Belgian control individuals revealed that one VCP SNP (rs565070) turned out to be associated with PDB in this Belgian study population (p = 5.5 x 10(-3)). None of the tag SNPs or MMTs selected for TNFSF11 or IL-6 was associated with PDB. Still, replication of our findings in the VCP gene in other populations is important to confirm our results. However, when combining data of VCP with those from other susceptible gene regions from previous association studies (i.e. TNFRSF11A, CSF1, OPTN and TM7SF4), independent effect of each gene region was found and the cumulative population attributable risk is 72.7%. (C) 2011 Elsevier Inc. All rights reserved.
Notes: [Chung, PYJ; Beyens, G; de Freitas, F; Van Hul, W] Univ Antwerp, Dept Med Genet, B-2610 Antwerp, Belgium [Boonen, S] Univ Louvain, Musculoskeletal Res Unit, Dept Expt Med, UZ Leuven, B-3000 Louvain, Belgium [Geusens, P] Univ Hasselt, Biomed Res Inst, B-3590 Diepenbeek, Belgium [Geusens, P] Univ Hosp, NL-6229 HX Maastricht, Netherlands [Vanhoenacker, F] Univ Antwerp Hosp, Dept Radiol, B-2650 Edegem, Belgium [Verbruggen, L] UZ Brussel, Dept Rheumatol, B-1090 Brussels, Belgium [Van Offel, J] Univ Hosp Antwerp UZA, Dept Immunol & Rheumatol, B-2650 Edegem, Belgium [Goemaere, S; Zmierczak, HG] Ghent Univ Hosp, Unit Osteoporosis & Metab Bone Dis, B-9000 Ghent, Belgium [Westhovens, R] UZ KULeuven, Dept Rheumatol, B-3000 Louvain, Belgium [Devogelaer, JP] Catholic Univ Louvain, Dept Rheumatol, St Luc Univ Hosp, B-1200 Brussels, Belgium wim.vanhul@ua.ac.be
URI: http://hdl.handle.net/1942/12062
DOI: 10.1016/j.ymgme.2011.03.021
ISI #: 000291919500013
ISSN: 1096-7192
Category: A1
Type: Journal Contribution
Validation: ecoom, 2012
Appears in Collections: Research publications

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