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COL1A1 Sp1 polymorphism predicts perimenopausal and early postmenopausal spinal bone loss

MacDonald, H M ; McGuigan, F A LU orcid ; New, S A ; Campbell, M K ; Golden, M H ; Ralston, S H and Reid, D M (2001) In Journal of Bone and Mineral Research 16(9). p.41-1634
Abstract

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 Spl binding site in the COLIA1 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 COLIA1 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 COLIA1 genotype, have yielded conflicting results. In this study, we examined the relationship between COLIA1 Sp1 alleles and early postmenopausal... (More)

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 Spl binding site in the COLIA1 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 COLIA1 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 COLIA1 genotype, have yielded conflicting results. In this study, we examined the relationship between COLIA1 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 (FN) 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 COLIA1 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.

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publishing date
type
Contribution to journal
publication status
published
keywords
Binding Sites, Bone Density, Climacteric, Cohort Studies, Collagen, Collagen Type I, Female, Femur Neck, Genetic Predisposition to Disease, Genetic Testing, Genotype, Hormone Replacement Therapy, Humans, Lumbar Vertebrae, Middle Aged, Osteoporosis, Postmenopausal, Polymorphism, Genetic, Population Surveillance, Postmenopause, Predictive Value of Tests, Sp1 Transcription Factor, Spine, Journal Article, Research Support, Non-U.S. Gov't
in
Journal of Bone and Mineral Research
volume
16
issue
9
pages
8 pages
publisher
Wiley-Blackwell
external identifiers
  • pmid:11547832
  • scopus:0034877199
ISSN
0884-0431
DOI
10.1359/jbmr.2001.16.9.1634
language
English
LU publication?
no
id
e8b665ba-3ce4-43f3-9682-a62c45f1ee18
date added to LUP
2018-01-02 11:06:25
date last changed
2024-01-14 10:13:31
@article{e8b665ba-3ce4-43f3-9682-a62c45f1ee18,
  abstract     = {{<p>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 Spl binding site in the COLIA1 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 COLIA1 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 COLIA1 genotype, have yielded conflicting results. In this study, we examined the relationship between COLIA1 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 &lt; 0.001 for both sites). There was no significant difference in baseline BMD values at the lumbar spine (LS) or femoral neck (FN) 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 COLIA1 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.</p>}},
  author       = {{MacDonald, H M and McGuigan, F A and New, S A and Campbell, M K and Golden, M H and Ralston, S H and Reid, D M}},
  issn         = {{0884-0431}},
  keywords     = {{Binding Sites; Bone Density; Climacteric; Cohort Studies; Collagen; Collagen Type I; Female; Femur Neck; Genetic Predisposition to Disease; Genetic Testing; Genotype; Hormone Replacement Therapy; Humans; Lumbar Vertebrae; Middle Aged; Osteoporosis, Postmenopausal; Polymorphism, Genetic; Population Surveillance; Postmenopause; Predictive Value of Tests; Sp1 Transcription Factor; Spine; Journal Article; Research Support, Non-U.S. Gov't}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{41--1634}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Journal of Bone and Mineral Research}},
  title        = {{COL1A1 Sp1 polymorphism predicts perimenopausal and early postmenopausal spinal bone loss}},
  url          = {{http://dx.doi.org/10.1359/jbmr.2001.16.9.1634}},
  doi          = {{10.1359/jbmr.2001.16.9.1634}},
  volume       = {{16}},
  year         = {{2001}},
}