Large-scale analysis of association between polymorphisms in the transforming growth factor beta 1 gene (TGFB1) and osteoporosis: The GENOMOS study

Langdahl, Bente L., Uitterlinden, André G., Ralston, Stuart H., Trikalinos, Thomas A., Balcells, Susanne, Brandi, Maria Luisa, Scollen, Serena, Lips, Paul, Lorenc, Roman, Obermayer-Pietsch, Barbara, Reid, David M., Armas, Jácome Bruges, Arp, Pascal P., Bassiti, Amelia, Bustamante, Mariona, Husted, Lise Bjerre, Carey, Alison H., Cano, Ramon Pérez, Dobnig, Harald, Dunning, Alison M., Fahrleitner-Pammer, Astrid, Falchetti, Alberto, Karczmarewicz, Elzbieta, Kruk, Marcin, van Leeuwen, Johannes P. T. M., Masi, Laura, van Meurs, Joyce B. J., Mangion, Jon, McGuigan, Fiona E .A., Mellibovsky, Leonardo, Mosekilde, Leif, Nogués, Xavier, Pols, Huibert A. P., Reeve, Jonathan, Renner, Wilfried, Rivadeneira, Fernando, van Schoor, Natasja M., Ioannidis, John P. A.., Duncan, Emma L., Aberdeen Prospective Osteoporosis Study (APOSS) Investigators, Danish Osteoporosis Prevention Study (DOPS) Investigators, European Prospective Osteoporosis Study (EPOS) Investigators, European Polish Osteoporosis Study (EPOLOS) Study, Familial Osteoporosis Study (FAMOS) Investigators, Longitudinal Aging Study Amsterdam (LASA) Investigators and Rotterdam Group (ERGO) Investigators (2008) Large-scale analysis of association between polymorphisms in the transforming growth factor beta 1 gene (TGFB1) and osteoporosis: The GENOMOS study. Bone, 42 5: 969-981. doi:10.1016/j.bone.2007.11.007


Author Langdahl, Bente L.
Uitterlinden, André G.
Ralston, Stuart H.
Trikalinos, Thomas A.
Balcells, Susanne
Brandi, Maria Luisa
Scollen, Serena
Lips, Paul
Lorenc, Roman
Obermayer-Pietsch, Barbara
Reid, David M.
Armas, Jácome Bruges
Arp, Pascal P.
Bassiti, Amelia
Bustamante, Mariona
Husted, Lise Bjerre
Carey, Alison H.
Cano, Ramon Pérez
Dobnig, Harald
Dunning, Alison M.
Fahrleitner-Pammer, Astrid
Falchetti, Alberto
Karczmarewicz, Elzbieta
Kruk, Marcin
van Leeuwen, Johannes P. T. M.
Masi, Laura
van Meurs, Joyce B. J.
Mangion, Jon
McGuigan, Fiona E .A.
Mellibovsky, Leonardo
Mosekilde, Leif
Nogués, Xavier
Pols, Huibert A. P.
Reeve, Jonathan
Renner, Wilfried
Rivadeneira, Fernando
van Schoor, Natasja M.
Ioannidis, John P. A..
Duncan, Emma L.
Aberdeen Prospective Osteoporosis Study (APOSS) Investigators
Danish Osteoporosis Prevention Study (DOPS) Investigators
European Prospective Osteoporosis Study (EPOS) Investigators
European Polish Osteoporosis Study (EPOLOS) Study
Familial Osteoporosis Study (FAMOS) Investigators
Longitudinal Aging Study Amsterdam (LASA) Investigators
Rotterdam Group (ERGO) Investigators
Title Large-scale analysis of association between polymorphisms in the transforming growth factor beta 1 gene (TGFB1) and osteoporosis: The GENOMOS study
Journal name Bone   Check publisher's open access policy
ISSN 8756-3282
1873-2763
Publication date 2008-05
Year available 2007
Sub-type Article (original research)
DOI 10.1016/j.bone.2007.11.007
Volume 42
Issue 5
Start page 969
End page 981
Total pages 13
Editor Roland Baron
Place of publication New York, U.S.A.
Publisher Elsevier
Language eng
Subject 1103 Clinical Sciences
Formatted abstract
Introduction
The TGFB1 gene which encodes transforming growth factor beta 1, is a strong candidate for susceptibility to osteoporosis and several studies have reported associations between bone mineral density (BMD), osteoporotic fractures and polymorphisms of TGFB1, although these studies have yielded conflicting results.

Methods
We investigated associations between TGFB1 polymorphisms and BMD and fracture in the GENOMOS study: a prospective multicenter study involving 10 European research studies including a total of 28,924 participants. Genotyping was conducted for known TGFB1 polymorphisms at the following sites: G− 1639-A (G− 800-A, rs1800468), C− 1348-T (C− 509-T, rs1800469), T29-C (Leu10Pro, rs1982073), G74-C (Arg25Pro, rs1800471) and C788-T (Thr263Ile, rs1800472). These polymorphisms were genotyped prospectively and methodology was standardized across research centers. Genotypes and haplotypes were related to BMD at the lumbar sine and femoral neck and fractures.

Results
There were no significant differences in either women or men at either skeletal site for any of the examined polymorphisms with the possible exception of a weak association with reduced BMD (− 12 mg/cm2) in men with the T− 1348 allele (p < 0.05). None of the haplotypes was associated with BMD and none of the polymorphisms or haplotypes significantly affected overall risk of fractures, however, the odds ratio for incident vertebral fracture in carriers of the rare T788 allele was 1.64 (95% CI: 1.09–2.64), p < 0.05.

Conclusions
This study indicates that polymorphic variation in the TGFB1 gene does not play a major role in regulating BMD or susceptibility to fractures. The weak associations we observed between the C− 1348-T and lumbar spine BMD in men and between C788-T and risk of incident vertebral fractures are of interest but could be chance findings and will need replication in future studies.
Copyright © 2007 Elsevier Inc.
Keyword Transforming growth factor beta 1
Fracture
Bone mineral density
Osteoporosis
Meta-analysis
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes Available online 3 December 2007.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
UQ Diamantina Institute Publications
 
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Created: Tue, 23 Feb 2010, 11:50:41 EST by Gerald Martin on behalf of UQ Diamantina Institute