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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 and Obermayer-Pietsch, Barbara, et al. (2008) In Bone 42(5). p.81-969
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,... (More)

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.

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Adult, Aged, Aged, 80 and over, Bone Density, Case-Control Studies, Cohort Studies, Cross-Sectional Studies, Female, Femur Neck, Fractures, Bone, Gene Frequency, Genotype, Humans, Logistic Models, Lumbar Vertebrae, Male, Middle Aged, Odds Ratio, Osteoporosis, Polymorphism, Single Nucleotide, Sex Factors, Spinal Fractures, Transforming Growth Factor beta1, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't
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Bone
volume
42
issue
5
pages
13 pages
publisher
Elsevier
external identifiers
  • scopus:41949128499
ISSN
8756-3282
DOI
10.1016/j.bone.2007.11.007
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English
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fe5261f6-b9eb-4ea8-97fa-a125f7bcba85
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2019-05-12 04:48:04
@article{fe5261f6-b9eb-4ea8-97fa-a125f7bcba85,
  abstract     = {<p>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.</p><p>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.</p><p>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&lt;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&lt;0.05.</p><p>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.</p>},
  author       = {Langdahl, Bente L and Uitterlinden, André G and Ralston, Stuart H and Trikalinos, Thomas A and Balcells, Susanne and Brandi, Maria Luisa and Scollen, Serena and Lips, Paul and Lorenc, Roman and Obermayer-Pietsch, Barbara and Reid, David M and Armas, Jácome Bruges and Arp, Pascal P and Bassiti, Amelia and Bustamante, Mariona and Husted, Lise Bjerre and Carey, Alison H and Pérez Cano, Ramon and Dobnig, Harald and Dunning, Alison M and Fahrleitner-Pammer, Astrid and Falchetti, Alberto and Karczmarewicz, Elzbieta and Kruk, Marcin and van Leeuwen, Johannes P T M and Masi, Laura and van Meurs, Joyce B J and Mangion, Jon and McGuigan, Fiona E A and Mellibovsky, Leonardo and Mosekilde, Leif and Nogués, Xavier and Pols, Huibert A P and Reeve, Jonathan and Renner, Wilfried and Rivadeneira, Fernando and van Schoor, Natasja M and Ioannidis, John P A and , },
  issn         = {8756-3282},
  keyword      = {Adult,Aged,Aged, 80 and over,Bone Density,Case-Control Studies,Cohort Studies,Cross-Sectional Studies,Female,Femur Neck,Fractures, Bone,Gene Frequency,Genotype,Humans,Logistic Models,Lumbar Vertebrae,Male,Middle Aged,Odds Ratio,Osteoporosis,Polymorphism, Single Nucleotide,Sex Factors,Spinal Fractures,Transforming Growth Factor beta1,Journal Article,Multicenter Study,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {5},
  pages        = {81--969},
  publisher    = {Elsevier},
  series       = {Bone},
  title        = {Large-scale analysis of association between polymorphisms in the transforming growth factor beta 1 gene (TGFB1) and osteoporosis : the GENOMOS study},
  url          = {http://dx.doi.org/10.1016/j.bone.2007.11.007},
  volume       = {42},
  year         = {2008},
}