title: Estrogen receptor beta polymorphisms are associated with bone mass in women and men: the Framingham Study.
abstract: ESR2 is expressed in bone cells, yet few studies have tested its variation for association with BMD, an important determinant of osteoporotic fractures. This was investigated in 723 men and 795 women from the Framingham study. Results show association of variation in this gene with BMD in both women and men.
  
  
  BACKGROUND
  Osteoporotic fracture risk is highly dependent on bone density, a quantitative multifactorial trait with a substantial genetic component. In contrast to the growing body of evidence that estrogen receptor alpha (ESR1) plays a role in bone metabolism, few studies have examined the estrogen receptor beta (ESR2) gene for association with BMD. An ESR2 CA repeat polymorphism, D14S1026, was associated with BMD in two small studies, each with <200 women.
  
  
  METHODS
  The objective of this investigation was to assess whether D14S1026 or four other intronic polymorphisms were associated with BMD in 723 men and 795 women (mean age, 60 years) from the offspring cohort of the population-based Framingham Study. BMD was measured at the femur (neck, trochanter, and Ward's area) and the lumbar spine (L(2)-L(4)).
  
  
  RESULTS
  In both women and men, there was significant association of D14S1026 genotype with measures of femoral but not spinal BMD. In addition, genotypes of two common single nucleotide polymorphisms, rs1256031 and rs1256059, in strong linkage disequilibrium with one another but not with D14S1026, were associated with measures of femoral BMD in men. The rs1256031 genotypes had up to a 4.0% difference in mean femoral BMD. An inferred rs1256031-D14S1026-rs1256059 haplotype C-23CA-T was significantly associated with reduced femoral BMD in women (p = 0.03, 0.003, and 0.01 for neck, trochanter, and Ward's area, respectively). Haplotype-based BMD differences ranged from 3.0% to 4.3%.
  
  
  CONCLUSIONS
  We have observed significant association of common ESR2 variants with measures of femoral BMD in both men and women.
authors.affiliation: Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Shearman
authors.forename: David
authors.initials: D
authors.lastname: Karasik
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Gruenthal
authors.forename: Serkalem
authors.initials: S
authors.lastname: Demissie
authors.forename: L Adrienne
authors.initials: LA
authors.lastname: Cupples
authors.forename: David E
authors.initials: DE
authors.lastname: Housman
authors.forename: Douglas P
authors.initials: DP
authors.lastname: Kiel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015519:Bone Density / Q000235:genetics*; D015331:Cohort Studies; D047629:Estrogen Receptor beta; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D011859:Radiography; D011960:Receptors, Estrogen / Q000235:genetics*; D012044:Regression Analysis
chemical_list: D047629:Estrogen Receptor beta; D011960:Receptors, Estrogen