Large-scale analysis of association between polymorphisms in the transfonning growth factor beta 1 gene (TGFB1) and osteoporosis

The GENOMOS study

Bente L. Langdahl, Andre G. Uitterlinden, Stuart H. Ralston, Thomas A. Trikalinos, Susanne Balcells, Maria Luisa Brandi, Serena Scollen, Paul Lips, Roman Lorenc, Barbara Obermayer-Pietsch, David M. Reid, Jacome Bruges Armas, Pascal P. Arp, Amelia Bassiti, Mariona Bustamante, Lise Bjerre Husted, Alison H. Carey, Ramon Perez Cano, Harald Dobnig, Alison M. Dunning & 19 others Astrid Fahrleitner-Pammer, Alberto Falchetti, Elzbieta Karczmarewicz, Marcin Kruk, Johannes P. T. M. van Leeuwen, Laura Masi, Joyce B. J. van Meurs, Jon Mangion, Fiona E. A. McGuigan, Leonardo Mellibovsky, Leif Mosekilde, Xavier Nogues, Huibert A. P. Pols, Jonathan Reeve, Wilfried Renner, Fernando Rivadeneira, Natasja M. van Schoor, John P. A. Ioannidis, ERGO Investigators, EPOLOS Investigators, FAMOS Investigators, LASA Investigators, EPOS Investigators, DOPS Investigators, GENOMOS Study, APOSS Investigators

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

Introduction: The TGFBI 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 TGFBI, although these studies have yielded conflicting results.

Methods: We investigated associations between TGFBI 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 TGFBI polymorphisms at the following sites: G(-1639) -A (G(-800) -A, rs1800468), C-1348-T (C-509-T, rs1800469), T-29-C (Leu10Pro, rs1982073), G(74)-C (Arg25Pro, rs1800471) and C-788-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 BNID (- 12 mg/m(2)) in men with the T-1348 allele (p < 0.05). Nine 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 T-788 allele was 1.64 (95% CI: 1.09-2.64), p < 0.05.

Conclusions: This study indicates that polymorphic variation in the TGFBI 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 C-788-T and risk of incident vertebral fractures are of interest but could be chance findings and will need replication in future studies. (c) 2007 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)969-981
Number of pages13
JournalBone
Volume42
Issue number5
Early online date3 Dec 2007
DOIs
Publication statusPublished - May 2008

Keywords

  • transforming growth factor beta 1
  • fracture
  • bone mineral density
  • osteoporosis
  • meta-analysis
  • bone-mineral density
  • Camurati-Engelmann-disease
  • growth-factor-beta
  • latency-associated peptide
  • Japanese women
  • quantitative ultrasound
  • vertebral deformity
  • SP1 polymorphism
  • clinical-trials
  • Vitamin-D

Cite this

Langdahl, B. L., Uitterlinden, A. G., Ralston, S. H., Trikalinos, T. A., Balcells, S., Brandi, M. L., ... ERGO Investigators, EPOLOS Investigators, FAMOS Investigators, LASA Investigators, EPOS Investigators, DOPS Investigators, GENOMOS Study, APOSS Investigators (2008). Large-scale analysis of association between polymorphisms in the transfonning growth factor beta 1 gene (TGFB1) and osteoporosis: The GENOMOS study. Bone, 42(5), 969-981. https://doi.org/10.1016/j.bone.2007.11.007

Large-scale analysis of association between polymorphisms in the transfonning growth factor beta 1 gene (TGFB1) and osteoporosis : The GENOMOS study. / Langdahl, Bente L.; Uitterlinden, Andre 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, Jacome Bruges; Arp, Pascal P.; Bassiti, Amelia; Bustamante, Mariona; Husted, Lise Bjerre; Carey, Alison H.; Cano, Ramon Perez; 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; Nogues, Xavier; Pols, Huibert A. P.; Reeve, Jonathan; Renner, Wilfried; Rivadeneira, Fernando; van Schoor, Natasja M.; Ioannidis, John P. A.; ERGO Investigators, EPOLOS Investigators, FAMOS Investigators, LASA Investigators, EPOS Investigators, DOPS Investigators, GENOMOS Study, APOSS Investigators.

In: Bone, Vol. 42, No. 5, 05.2008, p. 969-981.

Research output: Contribution to journalArticle

Langdahl, BL, Uitterlinden, AG, Ralston, SH, Trikalinos, TA, Balcells, S, Brandi, ML, Scollen, S, Lips, P, Lorenc, R, Obermayer-Pietsch, B, Reid, DM, Armas, JB, Arp, PP, Bassiti, A, Bustamante, M, Husted, LB, Carey, AH, Cano, RP, Dobnig, H, Dunning, AM, Fahrleitner-Pammer, A, Falchetti, A, Karczmarewicz, E, Kruk, M, van Leeuwen, JPTM, Masi, L, van Meurs, JBJ, Mangion, J, McGuigan, FEA, Mellibovsky, L, Mosekilde, L, Nogues, X, Pols, HAP, Reeve, J, Renner, W, Rivadeneira, F, van Schoor, NM, Ioannidis, JPA & ERGO Investigators, EPOLOS Investigators, FAMOS Investigators, LASA Investigators, EPOS Investigators, DOPS Investigators, GENOMOS Study, APOSS Investigators 2008, 'Large-scale analysis of association between polymorphisms in the transfonning growth factor beta 1 gene (TGFB1) and osteoporosis: The GENOMOS study', Bone, vol. 42, no. 5, pp. 969-981. https://doi.org/10.1016/j.bone.2007.11.007
Langdahl, Bente L. ; Uitterlinden, Andre 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, Jacome Bruges ; Arp, Pascal P. ; Bassiti, Amelia ; Bustamante, Mariona ; Husted, Lise Bjerre ; Carey, Alison H. ; Cano, Ramon Perez ; 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 ; Nogues, Xavier ; Pols, Huibert A. P. ; Reeve, Jonathan ; Renner, Wilfried ; Rivadeneira, Fernando ; van Schoor, Natasja M. ; Ioannidis, John P. A. ; ERGO Investigators, EPOLOS Investigators, FAMOS Investigators, LASA Investigators, EPOS Investigators, DOPS Investigators, GENOMOS Study, APOSS Investigators. / Large-scale analysis of association between polymorphisms in the transfonning growth factor beta 1 gene (TGFB1) and osteoporosis : The GENOMOS study. In: Bone. 2008 ; Vol. 42, No. 5. pp. 969-981.
@article{9ce8c685128b4c27bb484059296c7fbf,
title = "Large-scale analysis of association between polymorphisms in the transfonning growth factor beta 1 gene (TGFB1) and osteoporosis: The GENOMOS study",
abstract = "Introduction: The TGFBI 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 TGFBI, although these studies have yielded conflicting results.Methods: We investigated associations between TGFBI 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 TGFBI polymorphisms at the following sites: G(-1639) -A (G(-800) -A, rs1800468), C-1348-T (C-509-T, rs1800469), T-29-C (Leu10Pro, rs1982073), G(74)-C (Arg25Pro, rs1800471) and C-788-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 BNID (- 12 mg/m(2)) in men with the T-1348 allele (p < 0.05). Nine 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 T-788 allele was 1.64 (95{\%} CI: 1.09-2.64), p < 0.05.Conclusions: This study indicates that polymorphic variation in the TGFBI 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 C-788-T and risk of incident vertebral fractures are of interest but could be chance findings and will need replication in future studies. (c) 2007 Elsevier Inc. All rights reserved.",
keywords = "transforming growth factor beta 1, fracture, bone mineral density, osteoporosis, meta-analysis, bone-mineral density, Camurati-Engelmann-disease, growth-factor-beta, latency-associated peptide, Japanese women, quantitative ultrasound, vertebral deformity, SP1 polymorphism, clinical-trials, Vitamin-D",
author = "Langdahl, {Bente L.} and Uitterlinden, {Andre G.} and Ralston, {Stuart H.} and Trikalinos, {Thomas A.} and Susanne Balcells and Brandi, {Maria Luisa} and Serena Scollen and Paul Lips and Roman Lorenc and Barbara Obermayer-Pietsch and Reid, {David M.} and Armas, {Jacome Bruges} and Arp, {Pascal P.} and Amelia Bassiti and Mariona Bustamante and Husted, {Lise Bjerre} and Carey, {Alison H.} and Cano, {Ramon Perez} and Harald Dobnig and Dunning, {Alison M.} and Astrid Fahrleitner-Pammer and Alberto Falchetti and Elzbieta Karczmarewicz and Marcin Kruk and {van Leeuwen}, {Johannes P. T. M.} and Laura Masi and {van Meurs}, {Joyce B. J.} and Jon Mangion and McGuigan, {Fiona E. A.} and Leonardo Mellibovsky and Leif Mosekilde and Xavier Nogues and Pols, {Huibert A. P.} and Jonathan Reeve and Wilfried Renner and Fernando Rivadeneira and {van Schoor}, {Natasja M.} and Ioannidis, {John P. A.} and {ERGO Investigators, EPOLOS Investigators, FAMOS Investigators, LASA Investigators, EPOS Investigators, DOPS Investigators, GENOMOS Study, APOSS Investigators}",
year = "2008",
month = "5",
doi = "10.1016/j.bone.2007.11.007",
language = "English",
volume = "42",
pages = "969--981",
journal = "Bone",
issn = "8756-3282",
publisher = "Elsevier Inc.",
number = "5",

}

TY - JOUR

T1 - Large-scale analysis of association between polymorphisms in the transfonning growth factor beta 1 gene (TGFB1) and osteoporosis

T2 - The GENOMOS study

AU - Langdahl, Bente L.

AU - Uitterlinden, Andre 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, Jacome Bruges

AU - Arp, Pascal P.

AU - Bassiti, Amelia

AU - Bustamante, Mariona

AU - Husted, Lise Bjerre

AU - Carey, Alison H.

AU - Cano, Ramon Perez

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 - Nogues, 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 - ERGO Investigators, EPOLOS Investigators, FAMOS Investigators, LASA Investigators, EPOS Investigators, DOPS Investigators, GENOMOS Study, APOSS Investigators

PY - 2008/5

Y1 - 2008/5

N2 - Introduction: The TGFBI 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 TGFBI, although these studies have yielded conflicting results.Methods: We investigated associations between TGFBI 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 TGFBI polymorphisms at the following sites: G(-1639) -A (G(-800) -A, rs1800468), C-1348-T (C-509-T, rs1800469), T-29-C (Leu10Pro, rs1982073), G(74)-C (Arg25Pro, rs1800471) and C-788-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 BNID (- 12 mg/m(2)) in men with the T-1348 allele (p < 0.05). Nine 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 T-788 allele was 1.64 (95% CI: 1.09-2.64), p < 0.05.Conclusions: This study indicates that polymorphic variation in the TGFBI 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 C-788-T and risk of incident vertebral fractures are of interest but could be chance findings and will need replication in future studies. (c) 2007 Elsevier Inc. All rights reserved.

AB - Introduction: The TGFBI 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 TGFBI, although these studies have yielded conflicting results.Methods: We investigated associations between TGFBI 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 TGFBI polymorphisms at the following sites: G(-1639) -A (G(-800) -A, rs1800468), C-1348-T (C-509-T, rs1800469), T-29-C (Leu10Pro, rs1982073), G(74)-C (Arg25Pro, rs1800471) and C-788-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 BNID (- 12 mg/m(2)) in men with the T-1348 allele (p < 0.05). Nine 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 T-788 allele was 1.64 (95% CI: 1.09-2.64), p < 0.05.Conclusions: This study indicates that polymorphic variation in the TGFBI 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 C-788-T and risk of incident vertebral fractures are of interest but could be chance findings and will need replication in future studies. (c) 2007 Elsevier Inc. All rights reserved.

KW - transforming growth factor beta 1

KW - fracture

KW - bone mineral density

KW - osteoporosis

KW - meta-analysis

KW - bone-mineral density

KW - Camurati-Engelmann-disease

KW - growth-factor-beta

KW - latency-associated peptide

KW - Japanese women

KW - quantitative ultrasound

KW - vertebral deformity

KW - SP1 polymorphism

KW - clinical-trials

KW - Vitamin-D

U2 - 10.1016/j.bone.2007.11.007

DO - 10.1016/j.bone.2007.11.007

M3 - Article

VL - 42

SP - 969

EP - 981

JO - Bone

JF - Bone

SN - 8756-3282

IS - 5

ER -