Tests of linkage and/or association of TGF-beta1 and COL1A1 genes with bone mass

Osteoporos Int. 2005 Jan;16(1):86-92. doi: 10.1007/s00198-004-1650-1. Epub 2004 May 26.


Transforming growth factor beta 1 (TGF-beta1) is involved in bone metabolism and collagen type I alpha 1 (COL1A1) is the most abundant protein of bone matrix. Both have been considered as candidate genes for osteoporosis. In this study, we employed the transmission disequilibrium test (TDT) to examine the relationship between each of the two genes with bone mineral density (BMD) and bone mineral content (BMC) at the spine and hip in a sample of 1668 subjects from 387 Caucasian nuclear families. For the TGF-beta1 gene, three SNPs, SNP1, SNP2, and SNP4 (located in exon 1, intron 4 and intron 5, respectively) were tested and the minor allele frequencies were 30.9%, 2.1% and 27.0%, respectively. All eight possible haplotypes (TGF1-8) were observed. For the COL1A1 gene, the minor allele frequencies of SNP5, SNP6 and SNP8 (located in exon 1, intron 1, and exon 45, respectively) were 15.2%, 18.7%, 2.0%, respectively, and only six of eight potential haplotypes (COL1-6) were obtained. In the whole sample, total associations were observed between haplotype COL5 with spine BMD (P=0.027), haplotypes COL3 and TGF4 with hip BMC (P=0.002, 0.003, respectively). Within-family associations were found for spine BMD at haplotypes TGF4 (P=0.027) in female offspring families and TGF3 (P=0.021) in male offspring families. Further studies with denser markers and larger sample size are required to eventually define the relationship between these two genes with bone mass at the spine and hip.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Bone Density / genetics*
  • Collagen Type I / genetics*
  • Family Health
  • Female
  • Gene Frequency / genetics
  • Haplotypes / genetics
  • Hip
  • Humans
  • Linkage Disequilibrium / genetics*
  • Male
  • Middle Aged
  • Parents
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics
  • Spine / physiology
  • Transforming Growth Factor beta / genetics*
  • Transforming Growth Factor beta1


  • Collagen Type I
  • TGFB1 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • collagen type I, alpha 1 chain