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Susceptibility to osteoporotic fracture is determined by allelic variation at the Sp1 site, rather than other polymorphic sites at the COL1A1 locus

McGuigan, F E LU ; Reid, D M and Ralston, S H (2000) In Osteoporosis International 11(4). p.43-338
Abstract

Previous studies have identified an association between osteoporotic fracture and a polymorphism affecting a Sp1 binding site in the first intron of the collagen type I alpha 1 gene (COL1A1). It is currently unclear, however, whether this association is direct or the result of linkage disequilibrium with other polymorphisms situated nearby. In this study we analyzed the relationship between four well-characterized single-nucleotide polymorphisms at the COL1A1 locus and osteoporotic fracture in 93 patients with vertebral fracture and 88 age-matched controls randomly selected from the community. We studied a MspI polymorphism 26 kb upstream of the COLIA1 gene, the Sp1 binding site polymorphism in intron 1, a RsaI polymorphism in intron 5... (More)

Previous studies have identified an association between osteoporotic fracture and a polymorphism affecting a Sp1 binding site in the first intron of the collagen type I alpha 1 gene (COL1A1). It is currently unclear, however, whether this association is direct or the result of linkage disequilibrium with other polymorphisms situated nearby. In this study we analyzed the relationship between four well-characterized single-nucleotide polymorphisms at the COL1A1 locus and osteoporotic fracture in 93 patients with vertebral fracture and 88 age-matched controls randomly selected from the community. We studied a MspI polymorphism 26 kb upstream of the COLIA1 gene, the Sp1 binding site polymorphism in intron 1, a RsaI polymorphism in intron 5 and a MnlI polymorphism in exon 52. The Sp1 and RsaI polymorphisms were in strong linkage disequilibrium (chi 2 = 77.87, p < 0.001) and weaker linkage disequilibrium was detected between the Sp1 and MnlI polymorphisms (chi 2 = 5.54, p < 0.025). There was a significant association between COL1A1 haplotypes that included the Sp1 and RsaI polymorphisms and fracture (p < 0.05-0.001), but no association with haplotypes that included only the MspI and MnlI polymorphisms. This association with fracture was strongest when haplotypes were grouped by Sp1 alleles (chi 2 = 11.15, d.f. = 1; p = 0.001). Furthermore, logistic regression analysis showed that of all the polymorphisms tested, only the Sp1 binding site polymorphism acted as an independent predictor of fracture: odds ratio [95% CI] = 2.26 [1.09-4.69]. These data suggest that it is the Sp1 polymorphism rather than other polymorphisms at the COL1A1 locus which act as a marker for osteoporotic fractures.

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published
keywords
Absorptiometry, Photon, Aged, Bone Density, Collagen, Female, Genetic Predisposition to Disease, Humans, Osteoporosis, Postmenopausal, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Spinal Fractures, Journal Article, Research Support, Non-U.S. Gov't
in
Osteoporosis International
volume
11
issue
4
pages
6 pages
publisher
Springer
external identifiers
  • scopus:0034043309
ISSN
0937-941X
DOI
10.1007/s001980070123
language
English
LU publication?
no
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e356020b-8908-454d-9bee-a4b31317d7ef
date added to LUP
2018-01-02 11:12:47
date last changed
2018-05-29 10:52:06
@article{e356020b-8908-454d-9bee-a4b31317d7ef,
  abstract     = {<p>Previous studies have identified an association between osteoporotic fracture and a polymorphism affecting a Sp1 binding site in the first intron of the collagen type I alpha 1 gene (COL1A1). It is currently unclear, however, whether this association is direct or the result of linkage disequilibrium with other polymorphisms situated nearby. In this study we analyzed the relationship between four well-characterized single-nucleotide polymorphisms at the COL1A1 locus and osteoporotic fracture in 93 patients with vertebral fracture and 88 age-matched controls randomly selected from the community. We studied a MspI polymorphism 26 kb upstream of the COLIA1 gene, the Sp1 binding site polymorphism in intron 1, a RsaI polymorphism in intron 5 and a MnlI polymorphism in exon 52. The Sp1 and RsaI polymorphisms were in strong linkage disequilibrium (chi 2 = 77.87, p &lt; 0.001) and weaker linkage disequilibrium was detected between the Sp1 and MnlI polymorphisms (chi 2 = 5.54, p &lt; 0.025). There was a significant association between COL1A1 haplotypes that included the Sp1 and RsaI polymorphisms and fracture (p &lt; 0.05-0.001), but no association with haplotypes that included only the MspI and MnlI polymorphisms. This association with fracture was strongest when haplotypes were grouped by Sp1 alleles (chi 2 = 11.15, d.f. = 1; p = 0.001). Furthermore, logistic regression analysis showed that of all the polymorphisms tested, only the Sp1 binding site polymorphism acted as an independent predictor of fracture: odds ratio [95% CI] = 2.26 [1.09-4.69]. These data suggest that it is the Sp1 polymorphism rather than other polymorphisms at the COL1A1 locus which act as a marker for osteoporotic fractures.</p>},
  author       = {McGuigan, F E and Reid, D M and Ralston, S H},
  issn         = {0937-941X},
  keyword      = {Absorptiometry, Photon,Aged,Bone Density,Collagen,Female,Genetic Predisposition to Disease,Humans,Osteoporosis, Postmenopausal,Polymerase Chain Reaction,Polymorphism, Single Nucleotide,Spinal Fractures,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {4},
  pages        = {43--338},
  publisher    = {Springer},
  series       = {Osteoporosis International},
  title        = {Susceptibility to osteoporotic fracture is determined by allelic variation at the Sp1 site, rather than other polymorphic sites at the COL1A1 locus},
  url          = {http://dx.doi.org/10.1007/s001980070123},
  volume       = {11},
  year         = {2000},
}