title: Association of oestrogen receptor alpha gene polymorphisms with postmenopausal bone loss, bone mass, and quantitative ultrasound properties of bone.
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 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.
authors.affiliation: The Bone Research Group, Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen AB25 2ZD, UK.
authors.forename: O M E
authors.initials: OM
authors.lastname: Albagha
authors.forename: U
authors.initials: U
authors.lastname: Pettersson
authors.forename: A
authors.initials: A
authors.lastname: Stewart
authors.forename: F E A
authors.initials: FE
authors.lastname: McGuigan
authors.forename: H M
authors.initials: HM
authors.lastname: MacDonald
authors.forename: D M
authors.initials: DM
authors.lastname: Reid
authors.forename: S H
authors.initials: SH
authors.lastname: Ralston
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence; D015519:Bone Density / Q000235:genetics*; D001842:Bone and Bones / Q000000981:diagnostic imaging*; D017124:Conserved Sequence; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D006239:Haplotypes; D020249:Hormone Replacement Therapy; D006801:Humans; D051379:Mice; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000000981:diagnostic imaging / Q000208:ethnology / Q000235:genetics*; D011110:Polymorphism, Genetic; D051381:Rats; D012606:Scotland / Q000208:ethnology; D014463:Ultrasonography
chemical_list: D047628:Estrogen Receptor alpha
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