TY - JOUR
T1 - Large-scale analysis of association between polymorphisms in the transforming growth factor beta 1 gene (TGFB1) and osteoporosis
T2 - The GENOMOS study
AU - APOSS investigators
AU - DOPS investigators
AU - EPOS investigators
AU - EPOLOS investigators
AU - FAMOS investigators
AU - LASA investigators
AU - ERGO investigators
AU - Langdahl, Bente L.
AU - Uitterlinden, André G.
AU - Ralston, Stuart H.
AU - Trikalinos, Thomas A.
AU - Balcells, Susanne
AU - Brandi, Maria Luisa
AU - Scollen, Serena
AU - Lips, Paul
AU - Lorenc, Roman
AU - Obermayer-Pietsch, Barbara
AU - Reid, David M.
AU - Armas, Jácome Bruges
AU - Arp, Pascal P.
AU - Bassiti, Amelia
AU - Bustamante, Mariona
AU - Husted, Lise Bjerre
AU - Carey, Alison H.
AU - Pérez Cano, Ramon
AU - Dobnig, Harald
AU - Dunning, Alison M.
AU - Fahrleitner-Pammer, Astrid
AU - Falchetti, Alberto
AU - Karczmarewicz, Elzbieta
AU - Kruk, Marcin
AU - van Leeuwen, Johannes P.T.M.
AU - Masi, Laura
AU - van Meurs, Joyce B.J.
AU - Mangion, Jon
AU - McGuigan, Fiona E.A.
AU - Mellibovsky, Leonardo
AU - Mosekilde, Leif
AU - Nogués, Xavier
AU - Pols, Huibert A.P.
AU - Reeve, Jonathan
AU - Renner, Wilfried
AU - Rivadeneira, Fernando
AU - van Schoor, Natasja M.
AU - Ioannidis, John P.A.
AU - Hugens, W (Wendy)
N1 - © 2007 Elsevier Inc. All rights reserved
PY - 2008/5
Y1 - 2008/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=41949128499&partnerID=8YFLogxK
U2 - 10.1016/j.bone.2007.11.007
DO - 10.1016/j.bone.2007.11.007
M3 - Article
C2 - 18284942
AN - SCOPUS:41949128499
SN - 8756-3282
VL - 42
SP - 969
EP - 981
JO - Bone
JF - Bone
IS - 5
ER -
