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Association of oestrogen receptor alpha gene polymorphisms with postmenopausal bone loss, bone mass, and quantitative ultrasound properties of bone

Albagha, O M E ; Pettersson, U ; Stewart, A ; McGuigan, F E A LU ; MacDonald, H M ; Reid, D M and Ralston, S H (2005) In Journal of Medical Genetics 42(3). p.6-240
Abstract

BACKGROUND: The gene encoding oestrogen receptor alpha (ESR1) appears to regulate bone mineral density (BMD) and other determinants of osteoporotic fracture risk.

OBJECTIVE: To investigate the relation between common polymorphisms and haplotypes of the ESR1 gene and osteoporosis related phenotypes in a population based cohort of 3054 Scottish women.

RESULTS: There was a significant association between a common haplotype "px", defined by the PvuII and XbaI restriction fragment length polymorphisms within intron 1 of the ESR1 gene, and femoral neck bone loss in postmenopausal women who had not received hormone replacement therapy (n = 945; p = 0.009). Annual rates of femoral neck bone loss were approximately 14% higher in... (More)

BACKGROUND: The gene encoding oestrogen receptor alpha (ESR1) appears to regulate bone mineral density (BMD) and other determinants of osteoporotic fracture risk.

OBJECTIVE: To investigate the relation between common polymorphisms and haplotypes of the ESR1 gene and osteoporosis related phenotypes in a population based cohort of 3054 Scottish women.

RESULTS: There was a significant association between a common haplotype "px", defined by the PvuII and XbaI restriction fragment length polymorphisms within intron 1 of the ESR1 gene, and femoral neck bone loss in postmenopausal women who had not received hormone replacement therapy (n = 945; p = 0.009). Annual rates of femoral neck bone loss were approximately 14% higher in subjects who carried one copy of px and 22% higher in those who carried two copies, compared with those who did not carry the px haplotype. The px haplotype was associated with lower femoral neck BMD in the postmenopausal women (p = 0.02), and with reduced calcaneal broadband ultrasound attenuation (BUA) values in the whole study population (p = 0.005). There was no association between a TA repeat polymorphism in the ESR1 promoter and any phenotype studied, though on long range haplotype analysis subjects with a smaller number of TA repeats who also carried the px haplotype had reduced BUA values.

CONCLUSIONS: The ESR1px haplotype is associated with reduced hip BMD values and increased rates of femoral neck bone loss in postmenopausal women. An association with BUA may explain the fact that ESR1 intron 1 alleles predict osteoporotic fractures by a mechanism partly independent of differences in BMD.

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publishing date
type
Contribution to journal
publication status
published
keywords
Alleles, Animals, Base Sequence, Bone Density, Bone and Bones, Conserved Sequence, Estrogen Receptor alpha, Female, Gene Frequency, Genetic Testing, Haplotypes, Hormone Replacement Therapy, Humans, Mice, Middle Aged, Osteoporosis, Postmenopausal, Polymorphism, Genetic, Rats, Scotland, Ultrasonography, Journal Article, Research Support, Non-U.S. Gov't
in
Journal of Medical Genetics
volume
42
issue
3
pages
7 pages
publisher
BMJ Publishing Group
external identifiers
  • pmid:15744038
  • scopus:15044349602
ISSN
0022-2593
DOI
10.1136/jmg.2004.023895
language
English
LU publication?
no
id
67c386ca-cfb6-4cdd-bf47-37bf253b71c6
date added to LUP
2018-01-02 11:02:57
date last changed
2020-11-22 07:11:39
@article{67c386ca-cfb6-4cdd-bf47-37bf253b71c6,
  abstract     = {<p>BACKGROUND: The gene encoding oestrogen receptor alpha (ESR1) appears to regulate bone mineral density (BMD) and other determinants of osteoporotic fracture risk.</p><p>OBJECTIVE: To investigate the relation between common polymorphisms and haplotypes of the ESR1 gene and osteoporosis related phenotypes in a population based cohort of 3054 Scottish women.</p><p>RESULTS: There was a significant association between a common haplotype "px", defined by the PvuII and XbaI restriction fragment length polymorphisms within intron 1 of the ESR1 gene, and femoral neck bone loss in postmenopausal women who had not received hormone replacement therapy (n = 945; p = 0.009). Annual rates of femoral neck bone loss were approximately 14% higher in subjects who carried one copy of px and 22% higher in those who carried two copies, compared with those who did not carry the px haplotype. The px haplotype was associated with lower femoral neck BMD in the postmenopausal women (p = 0.02), and with reduced calcaneal broadband ultrasound attenuation (BUA) values in the whole study population (p = 0.005). There was no association between a TA repeat polymorphism in the ESR1 promoter and any phenotype studied, though on long range haplotype analysis subjects with a smaller number of TA repeats who also carried the px haplotype had reduced BUA values.</p><p>CONCLUSIONS: The ESR1px haplotype is associated with reduced hip BMD values and increased rates of femoral neck bone loss in postmenopausal women. An association with BUA may explain the fact that ESR1 intron 1 alleles predict osteoporotic fractures by a mechanism partly independent of differences in BMD.</p>},
  author       = {Albagha, O M E and Pettersson, U and Stewart, A and McGuigan, F E A and MacDonald, H M and Reid, D M and Ralston, S H},
  issn         = {0022-2593},
  language     = {eng},
  number       = {3},
  pages        = {6--240},
  publisher    = {BMJ Publishing Group},
  series       = {Journal of Medical Genetics},
  title        = {Association of oestrogen receptor alpha gene polymorphisms with postmenopausal bone loss, bone mass, and quantitative ultrasound properties of bone},
  url          = {http://dx.doi.org/10.1136/jmg.2004.023895},
  doi          = {10.1136/jmg.2004.023895},
  volume       = {42},
  year         = {2005},
}