Influence of Estrogen Receptor Alpha Polymorphism on Bone Mineral Density in Iranian Children

Hum Hered. 2019;84(2):82-89. doi: 10.1159/000502230. Epub 2019 Oct 25.


Background: Bone mass acquisition in childhood is directly linked to adult bone mineral density (BMD) and fracture risk. BMD is a heritable trait, more than 70% of its variability among a population is affected by genetic factors.

Objectives: In the present study, we wanted to investigate the association between estrogen receptor alpha (ESR1) polymorphisms, PvuII (rs2234693) and XbaI (rs9340799), and bone area, bone mineral content (BMC), and BMD of the lumbar spine, femoral neck, and also of the total body less the head in Iranian children.

Methods: The ESR1 gene PvuII and XbaI genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. Bone area, BMC, BMD, and bone mineral apparent density (BMAD) were assessed by dual-energy X-ray absorptiometry (DEXA). Linear regression was carried out to examine the effects of the ESR1 (PvuII and XbaI) polymorphisms on DEXA outputs when adjusted for confounding factors (i.e., age, sex, BMI, and pubertal stage) in 3 models.

Results: ESR1 (PvuII) gene polymorphisms (CT vs. CC) showed significant effects on the BMC of the total body less the head in all 3 models. For ESR1 (XbaI), individuals with the AG genotype had higher lumbar spine BMD and lumbar spine BMAD compared to other genotypes.

Conclusions: It seems that the PvuII and XbaI polymorphisms of ESR1 could be associated with BMC and BMD variation in Iranian children and adolescents.

Keywords: Bone mineral density; Children; Estrogen receptor alpha; Osteoporosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorptiometry, Photon
  • Adolescent
  • Alkaline Phosphatase / blood
  • Bone Density / genetics*
  • Calcium / blood
  • Child
  • Estrogen Receptor alpha / genetics*
  • Female
  • Gene Frequency / genetics
  • Humans
  • Iran
  • Male
  • Phosphorus / blood
  • Polymorphism, Single Nucleotide / genetics*
  • Regression Analysis
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood


  • ESR1 protein, human
  • Estrogen Receptor alpha
  • Vitamin D
  • Phosphorus
  • 25-hydroxyvitamin D
  • Alkaline Phosphatase
  • Calcium