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

Fiona Elizabeth Anne McGuigan, Helen M. Macdonald, Daisy Amelia Bassiti, Rosemary Farmer, Stuart Bear, Alison Stewart, Alison J Black, William D. Fraser, Findlay Welsh, David M. Reid, S Ralston

Research output: Contribution to journalArticle

17 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)195-202
Number of pages8
JournalJournal of Bone and Mineral Research
Issue number2
Early online date23 Oct 2006
Publication statusPublished - Feb 2007


  • genetic
  • polymorphism
  • TGFB1
  • BMD
  • fracture
  • bone-mineral density
  • transforming growth factor-beta-1-gene
  • hormone replacement therapy
  • Camurati-Engelmann-disease
  • growth-factor-beta
  • quantitative ultrasound
  • postmenopausal women
  • Japanese women
  • osteoporosis
  • turnover


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