Genetic Variation in the TNFRSF11A Gene Encoding RANK Is Associated With Susceptibility to Paget's Disease of Bone

Pui Yan Jenny Chung, Greet Beyens, Philip L. Riches, Liesbeth Van Wesenbeeck, Fenna de Freitas, Karen Jennes, Anna Daroszewska, Erik Fransen, Steven Boonen, Piet Geusens, Filip Vanhoenacker, Leon Verbruggen, Jan Van Offel, Stefan Goemaere, Hans-Georg Zmierczak, Rene Westhovens, Marcel Karperien, Socrates Papapoulos, Stuart H. Ralston, Jean-Pierre DevogelaerWim Van Hul*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

28 Citations (Web of Science)

Abstract

RANK (receptor activator of nuclear factor-?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 3.17?10(-4) , with the major effect coming from females. Moreover, 6 SNPs and 1 MMT withstood the Bonferroni correction (p?
Original languageEnglish
Pages (from-to)2592–2605
JournalJournal of Bone and Mineral Research
Volume25
Issue number12
DOIs
Publication statusPublished - Dec 2010

Keywords

  • TNFRSF11A
  • RANK
  • PAGET'S DISEASE OF BONE
  • GENETIC VARIANTS
  • SEX-DEPENDENT EFFECT

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