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 Devogelaer; Wim Van Hul

doi:10.1002/jbmr.162

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 journal › Article › Academic › peer-review

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 language	English
Pages (from-to)	2592–2605
Journal	Journal of Bone and Mineral Research
Volume	25
Issue number	12
DOIs	https://doi.org/10.1002/jbmr.162
Publication status	Published - Dec 2010

Keywords

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

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10.1002/jbmr.162

Cite this

Chung, P. Y. J., Beyens, G., Riches, P. L., Van Wesenbeeck, L., de Freitas, F., Jennes, K., Daroszewska, A., Fransen, E., Boonen, S., Geusens, P., Vanhoenacker, F., Verbruggen, L., Van Offel, J., Goemaere, S., Zmierczak, H.-G., Westhovens, R., Karperien, M., Papapoulos, S., Ralston, S. H., ... Van Hul, W. (2010). Genetic Variation in the TNFRSF11A Gene Encoding RANK Is Associated With Susceptibility to Paget's Disease of Bone. Journal of Bone and Mineral Research, 25(12), 2592–2605. https://doi.org/10.1002/jbmr.162

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

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?",

keywords = "TNFRSF11A, RANK, PAGET'S DISEASE OF BONE, GENETIC VARIANTS, SEX-DEPENDENT EFFECT",

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

year = "2010",

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Chung, PYJ, Beyens, G, Riches, PL, Van Wesenbeeck, L, de Freitas, F, Jennes, K, Daroszewska, A, Fransen, E, Boonen, S, Geusens, P, Vanhoenacker, F, Verbruggen, L, Van Offel, J, Goemaere, S, Zmierczak, H-G, Westhovens, R, Karperien, M, Papapoulos, S, Ralston, SH, Devogelaer, J-P & Van Hul, W 2010, 'Genetic Variation in the TNFRSF11A Gene Encoding RANK Is Associated With Susceptibility to Paget's Disease of Bone', Journal of Bone and Mineral Research, vol. 25, no. 12, pp. 2592–2605. https://doi.org/10.1002/jbmr.162

TY - JOUR

T1 - Genetic Variation in the TNFRSF11A Gene Encoding RANK Is Associated With Susceptibility to Paget's Disease of Bone

AU - Chung, Pui Yan Jenny

AU - Beyens, Greet

AU - Riches, Philip L.

AU - Van Wesenbeeck, Liesbeth

AU - de Freitas, Fenna

AU - Jennes, Karen

AU - Daroszewska, Anna

AU - Fransen, Erik

AU - Boonen, Steven

AU - Geusens, Piet

AU - Vanhoenacker, Filip

AU - Verbruggen, Leon

AU - Van Offel, Jan

AU - Goemaere, Stefan

AU - Zmierczak, Hans-Georg

AU - Westhovens, Rene

AU - Karperien, Marcel

AU - Papapoulos, Socrates

AU - Ralston, Stuart H.

AU - Devogelaer, Jean-Pierre

AU - Van Hul, Wim

PY - 2010/12

Y1 - 2010/12

N2 - 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?

AB - 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?

KW - TNFRSF11A

KW - RANK

KW - PAGET'S DISEASE OF BONE

KW - GENETIC VARIANTS

KW - SEX-DEPENDENT EFFECT

U2 - 10.1002/jbmr.162

DO - 10.1002/jbmr.162

M3 - Article

C2 - 20564239

SN - 0884-0431

VL - 25

SP - 2592

EP - 2605

JO - Journal of Bone and Mineral Research

JF - Journal of Bone and Mineral Research

IS - 12

ER -