Document Server@UHasselt >
Research >
Research publications >

Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/11458

Title: Genetic Variation in the TNFRSF11A Gene Encoding RANK Is Associated With Susceptibility to Paget's Disease of Bone
Authors: Chung, Pui Yan Jenny
Beyens, Greet
Riches, Philip L.
Van Wesenbeeck, Liesbeth
de Freitas, Fenna
Jennes, Karen
Daroszewska, Anna
Fransen, Erik
Boonen, Steven
Vanhoenacker, Filip
Verbruggen, Leon
Van Offel, Jan
Goemaere, Stefan
Zmierczak, Hans-Georg
Westhovens, Rene
Karperien, Marcel
Papapoulos, Socrates
Ralston, Stuart H.
Devogelaer, Jean-Pierre
Van Hul, Wim
Issue Date: 2010
Citation: JOURNAL OF BONE AND MINERAL RESEARCH, 25 (12). p. 2316-2329
Abstract: RANK (receptor activator of nuclear factor-kappa B), encoded by TNFRSF11A, is a key protein in osteoclastogenesis TNFRSF11A mutations cause Paget's disease of bone (PDB)-like diseases (ie, familial expansile osteolysis, expansile skeletal hyperphosphatasia, and early-onset PDB) and an osteoclast-poor form of osteopetrosis However, no TNFRSF11A mutations have been found in classic PDB, neither in familial nor in isolated cases To investigate the possible relationship between TNFRSF11A polymorphisms and sporadic PDB, we conducted an association study including 32 single-nucleotide polymorphisms (SNPs) in 196 Belgian sporadic PDB patients and 212 control individuals Thirteen SNPs and 3 multimarker tests (MMTs) turned out to have a p value of between 036 and 317 x 10(-4), with the major effect coming from females Moreover, 6 SNPs and 1 MMT withstood the Bonferroni correction (p < 002) Replication studies were performed for 2 nonsynonymous SNPs (rs35211496 and rs1805034) in a Dutch and a British cohort Interestingly, both SNPs resulted in p values ranging from 013 to 838 x 10(-5) in both populations Meta-analysis over three populations resulted in p = 002 for rs35211496 and p = 1 27 x 10(-8) for rs1805034, again mainly coming from the female subgroups In an attempt to identify the underlying causative SNP, we performed functional studies for the coding SNPs as well as resequencing efforts of a 31-kb region harboring a risk haplotype within the Belgian females However, neither approach resulted in significant evidence for the causality of any of the tested genetic variants Therefore, further studies are needed to identify the real cause of the increased risk to develop PDB shown to be present within TNFRSF11A (C) 2010 American Society for Bone and Mineral Research
Notes: [Chung, Pui Yan Jenny; Beyens, Greet; Van Wesenbeeck, Liesbeth; de Freitas, Fenna; Jennes, Karen; Fransen, Erik] Univ & Univ Hosp Antwerp, Dept Med Genet, Antwerp, Belgium. [Riches, Philip L.; Daroszewska, Anna; Ralston, Stuart H.] Univ Edinburgh, Rheumat Dis Unit, Mol Med Ctr, Edinburgh, Midlothian, Scotland. [Boonen, Steven] Leuven Univ, Musculoskeletal Res Unit, Dept Expt Med, Louvain, Belgium. [Boonen, Steven] UZ Leuven, Louvain, Belgium. [Geusens, Piet] Univ Hasselt, Biomed Res Inst, Diepenbeek, Belgium. [Geusens, Piet] Univ Hosp, Maastricht, Netherlands. [Vanhoenacker, Filip] Univ Antwerp Hosp, Dept Radiol, Antwerp, Belgium. [Verbruggen, Leon] UZ Brussel, Dept Rheumatol, Brussels, Belgium. [Van Offel, Jan] Univ Antwerp Hosp, Dept Immunol & Rheumatol, Antwerp, Belgium. [Zmierczak, Hans-Georg] Ghent Univ Hosp, Unit Osteoporosis & Metab Bone Dis, Ghent, Belgium. [Westhovens, Rene] UZ KULeuven, Dept Rheumatol, Leuven, Belgium. [Karperien, Marcel] Univ Twente, Dept Tissue Regenerat, NL-7500 AE Enschede, Netherlands. [Papapoulos, Socrates] Leiden Univ, Med Ctr, Leiden, Netherlands. [Devogelaer, Jean-Pierre] Catholic Univ Louvain, Dept Rheumatol, St Luc Univ Hosp, B-1200 Brussels, Belgium.
URI: http://hdl.handle.net/1942/11458
DOI: 10.1002/jbmr.162
ISI #: 000285080200006
ISSN: 0884-0431
Category: A1
Type: Journal Contribution
Validation: ecoom, 2012
Appears in Collections: Research publications

Files in This Item:

There are no files associated with this item.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.