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Large-scale population-based study shows no association between common polymorphisms of the TGFB1 gene and BMD in women

McGuigan, Fiona LU ; Macdonald, Helen M.; Bassiti, Amelia; Farmer, Rosemary; Bear, Stuart; Stewart, Alison; Black, Alison; Fraser, William D.; Welsh, Findlay and Reid, David M., et al. (2007) In Journal of Bone and Mineral Research 22(2). p.195-202
Abstract
Introduction: The gene encoding TGFBI is a strong functional candidate for genetic susceptibility to osteoporosis. Several polymorphisms have been identified in TGFB1, and previous work has suggested that allelic variants of TGFBI. may regulate BMD and susceptibility to osteoporotic fracture. Materials and Methods: We studied the relationship between common polymorphisms of TGFBI and several osteoporosis-related phenotypes including BMD at the lumbar spine and femoral neck, measured by DXA; bone loss over a 6-year period; biochemical markers of bone turnover (urinary free deoxypyridinoline and free pyridinoline/creatinine ratio and serum N-terminal propeptide of type 1 collagen), and fractures in a population-based study of 2975 women from... (More)
Introduction: The gene encoding TGFBI is a strong functional candidate for genetic susceptibility to osteoporosis. Several polymorphisms have been identified in TGFB1, and previous work has suggested that allelic variants of TGFBI. may regulate BMD and susceptibility to osteoporotic fracture. Materials and Methods: We studied the relationship between common polymorphisms of TGFBI and several osteoporosis-related phenotypes including BMD at the lumbar spine and femoral neck, measured by DXA; bone loss over a 6-year period; biochemical markers of bone turnover (urinary free deoxypyridinoline and free pyridinoline/creatinine ratio and serum N-terminal propeptide of type 1 collagen), and fractures in a population-based study of 2975 women from the United Kingdom. Participants were genotyped for single nucleotide polymorphisms (SNPs) in the TGFB1 promoter(G-800A; rs1800468; C-509T; rs1800469), exon 1 (T29C; rs1982073 and G74C; rs1982073); and exon 5 (C788T; rs1800471) on PCR-generated fragments of genomic DNA. Haplotypes were constructed from genotype data using the PHASE software program, and genotypes and haplotypes were related to the phenotypes of interest using general linear model ANOVA, with correction for confounding factors including age, height, weight, menopausal status, hormone replacement therapy (HRT) use, physical activity score, and dietary calcium intake. Results: The polymorphisms were in strong linkage disequilibrium, and four common haplotypes accounted for > 95% of alleles at the locus. There was no association between individual SNPs and BMD, bone loss, or biochemical markers of bone turnover. Haplotype analysis showed a nominally significant association with femoral neck BMD (p = 0.042) and with incident osteoporotic fracture (p = 0.013), but these were not significant after correcting for multiple testing. Conclusions: Common polymorphic variants of the TGFBI gene did not influence BMD or bone loss in this population. (Less)
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publication status
published
subject
keywords
fracture, TGFB1, genetic, polymorphism, BMD
in
Journal of Bone and Mineral Research
volume
22
issue
2
pages
195 - 202
publisher
AMBMR
external identifiers
  • wos:000243668800003
  • scopus:33846543136
ISSN
1523-4681
DOI
10.1359/jbmr.061016
language
English
LU publication?
yes
id
c6f8010d-592a-465e-abfe-d497fb9bc7b0 (old id 676597)
date added to LUP
2007-12-15 14:22:38
date last changed
2017-01-01 04:57:45
@article{c6f8010d-592a-465e-abfe-d497fb9bc7b0,
  abstract     = {Introduction: The gene encoding TGFBI is a strong functional candidate for genetic susceptibility to osteoporosis. Several polymorphisms have been identified in TGFB1, and previous work has suggested that allelic variants of TGFBI. may regulate BMD and susceptibility to osteoporotic fracture. Materials and Methods: We studied the relationship between common polymorphisms of TGFBI and several osteoporosis-related phenotypes including BMD at the lumbar spine and femoral neck, measured by DXA; bone loss over a 6-year period; biochemical markers of bone turnover (urinary free deoxypyridinoline and free pyridinoline/creatinine ratio and serum N-terminal propeptide of type 1 collagen), and fractures in a population-based study of 2975 women from the United Kingdom. Participants were genotyped for single nucleotide polymorphisms (SNPs) in the TGFB1 promoter(G-800A; rs1800468; C-509T; rs1800469), exon 1 (T29C; rs1982073 and G74C; rs1982073); and exon 5 (C788T; rs1800471) on PCR-generated fragments of genomic DNA. Haplotypes were constructed from genotype data using the PHASE software program, and genotypes and haplotypes were related to the phenotypes of interest using general linear model ANOVA, with correction for confounding factors including age, height, weight, menopausal status, hormone replacement therapy (HRT) use, physical activity score, and dietary calcium intake. Results: The polymorphisms were in strong linkage disequilibrium, and four common haplotypes accounted for > 95% of alleles at the locus. There was no association between individual SNPs and BMD, bone loss, or biochemical markers of bone turnover. Haplotype analysis showed a nominally significant association with femoral neck BMD (p = 0.042) and with incident osteoporotic fracture (p = 0.013), but these were not significant after correcting for multiple testing. Conclusions: Common polymorphic variants of the TGFBI gene did not influence BMD or bone loss in this population.},
  author       = {McGuigan, Fiona and Macdonald, Helen M. and Bassiti, Amelia and Farmer, Rosemary and Bear, Stuart and Stewart, Alison and Black, Alison and Fraser, William D. and Welsh, Findlay and Reid, David M. and Ralston, Stuart H.},
  issn         = {1523-4681},
  keyword      = {fracture,TGFB1,genetic,polymorphism,BMD},
  language     = {eng},
  number       = {2},
  pages        = {195--202},
  publisher    = {AMBMR},
  series       = {Journal of Bone and Mineral Research},
  title        = {Large-scale population-based study shows no association between common polymorphisms of the TGFB1 gene and BMD in women},
  url          = {http://dx.doi.org/10.1359/jbmr.061016},
  volume       = {22},
  year         = {2007},
}