COL1A1 Sp1 polymorphism predicts perimenopausal and early postmenopausal spinal bone loss

Helen Margaret MacDonald, Fiona Elizabeth Anne McGuigan, Marion Kay Campbell, David M Reid, S. A. New, Michael Henry Niven Golden, S Ralston

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68 Citations (Scopus)


Genetic factors play an important role in the pathogenesis of osteoporosis but the genes that determine susceptibility to poor bone health are defined incompletely. Previous work has shown that a polymorphism that affects an Sp1 binding site in the COL1A1 gene is associated with reduced bone mineral density (BMD) and an increased risk of osteoporotic fracture in several populations. Data from cross-sectional studies have indicated that COL1A1 Sp1 alleles also may be associated with increased rates of bone loss with age, but longitudinal studies, which have examined bone loss in relation to COL1A1 genotype, have yielded conflicting results. In this study, we examined the relationship between COL1A1 Sp1 alleles and early postmenopausal bone loss measured by dual-energy X-ray absorptiometry (DXA) in a population-based cohort of 734 Scottish women who were followed up over a 5- to 7-year period. The distribution of genotypes was as expected in a white population with 484 "SS" homozygotes (65.9%); 225 "Ss" heterozygotes (30.7%), and 25 "ss" homozygotes (3.4%). Women taking hormone-replacement therapy (HRT, n = 239) had considerably reduced rates of bone loss at the spine (-0.40 +/- 0.06%/year) and hip (-0.56 +/- 0.06%/year) when compared with non-HRT users (n = 352; spine, -1.36 +/- 0.06%/year; hip, -1.21 +/- 0.05%/year, p < 0.001 for both sites). There was no significant difference in baseline BMD values at the lumbar spine (LS) or femoral neck TM between genotypes or in the rates of bone loss between genotypes in HRT users. However, in non-HRT users (n = 352), we found that ss homozygotes (n = 12) lost significantly more bone at the lumbar site than the other genotype groups in which ss = -2.26 +/- 0.31%/year compared with SS = -1.38 +/- 0.07%/year and Ss = -1.22 +/- 0.10%/year (p = 0.004; analysis of variance [ANOVA]) and a similar trend was observed at the FN in which ss = -1.78 +/- 0.19%/year compared with SS = -1.21 +/- 0.06%/year and Ss = -1.16 +/- 0.08%/year (p = 0.06; ANOVA). The differences in spine BMD loss remained significant after correcting for confounding factors. Stepwise multiple regression analysis showed that COL1A1 genotype independently accounted for a further 3.0% of the variation in spine BMD change after age (4.0%), weight (5.0%), and baseline BMD (2.8%). We conclude that women homozygous for the Sp1 polymorphism are at significantly increased risk of excess rates of bone loss at the spine, but this effect may be nullified by the use of HRT.

Original languageEnglish
Pages (from-to)1634-1641
Number of pages7
JournalJournal of Bone and Mineral Research
Issue number9
Publication statusPublished - 2001


  • COL1A1 polymorphism
  • postmenopausal women
  • hormone replacement therapy
  • bone mineral density
  • bone loss
  • receptor gene polymorphism
  • binding-site polymorphism
  • mineral density
  • Vitamin-D
  • premenopausal women
  • osteoporotic fractures
  • regional osteoperosis
  • recruitment methods
  • screening programs


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