Estrogen receptor α gene polymorphisms and bone mineral density: Haplotype analysis in women from the United Kingdom

Omar Al Bagha, F. E.A. McGuigan, D. M. Reid, S. H. Ralston

Research output: Contribution to journalArticle

155 Citations (Scopus)

Abstract

Genetic factors are important in the pathogenesis of osteoporosis and the estrogen receptor has been suggested as a possible candidate gene for regulation of bone mineral density (BMD). We investigated the relationship between PvuII, XbaI, and dinucleotide (TA)n repeat polymorphisms of the estrogen receptor α (ER-α) gene and BMD in a study of women from northeast Scotland in the United Kingdom. No significant association was observed between BMD values at the lumbar spine (LS) and femoral neck (FN) in relation to PvuII and XbaI polymorphisms individually, but haplotype analysis showed that BMD values (Z score) were significantly lower in those who carried the Px haplotype (n = 36) compared with those who did not (n = 170) at both the LS (mean ± SEM; -0.775 ± 0.125 vs. -0.285 ± 0.082; p = 0.002) and the FN (-0.888 ± 0.130 vs. -0.335 ± 0.083; p = 0.0006). In keeping with this, the Px haplotype also was found to be an independent predictor of LS BMD (p = 0.019) and FN BMD (p = 0.005) in a multiple regression analysis model that included other possible predictors of BMD including age, years since menopause (YSM), hormone-replacement therapy (HRT) use, weight, and height. This model explained 15.7% and 23.4% of the total observed variance in LS and FN BMD, respectively, with the Px haplotype accounting for ∼3% of the variance at both sites. Although the TA repeat polymorphism was in strong linkage disequilibrium (LD) with the PvuII (χ2 = 109.8; p < 0.0001) and XbaI (χ2 = 97.2; p < 0.0001) polymorphisms, there was no overall association between TA repeat number and BMD. We conclude that polymorphisms of the ER-α gene are significantly related to BMD in our population and that this association is dependent on the Px haplotype, suggesting that it is the Px haplotype, or a linked polymorphism, that confers risk. (J Bone Miner Res 2001;16:128-134).

Original languageEnglish
Pages (from-to)128-134
Number of pages7
JournalJournal of Bone and Mineral Research
Volume16
Issue number1
Publication statusPublished - 2001
Externally publishedYes

Fingerprint

Estrogen Receptors
Bone Density
Haplotypes
Genes
Femur Neck
Spine
United Kingdom
Hormone Replacement Therapy
Linkage Disequilibrium
Scotland
Menopause
Osteoporosis
Regression Analysis
Weights and Measures
Bone and Bones

Keywords

  • Bone mineral density
  • Estrogen receptor
  • Genetic
  • Osteoporosis
  • Polymorphism

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

Cite this

Estrogen receptor α gene polymorphisms and bone mineral density : Haplotype analysis in women from the United Kingdom. / Al Bagha, Omar; McGuigan, F. E.A.; Reid, D. M.; Ralston, S. H.

In: Journal of Bone and Mineral Research, Vol. 16, No. 1, 2001, p. 128-134.

Research output: Contribution to journalArticle

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