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

Omar Albagha, Fiona Elizabeth Anne McGuigan, David M Reid, S 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 alpha (ER-alpha) 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 Pr 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 Pr haplotype accounting for similar to3% of the variance at both sites. Although the TA repeat polymorphism was in strong linkage disequilibrium (LD) with the PvuII (chi (2) = 109.8; p < 0.0001) and XbaI (<chi>(2) = 97.2; p < 0.0001) polymorphisms, there was no overall association between TA repeat number and BMD. We conclude that polymorphisms of the ER-<alpha> gene are significantly related to BMD) in our population and that this association is dependent on the Pr haplotype, suggesting that it is the Pr haplotype, or a linked polymorphism, that confers risk.

Original languageEnglish
Pages (from-to)128-134
Number of pages6
JournalJournal of Bone and Mineral Research
Volume16
Issue number1
DOIs
Publication statusPublished - 2001

Keywords

  • estrogen receptor
  • bone mineral density
  • genetic
  • polymorphism
  • osteoporosis
  • postmenopausal women
  • vitamin-D
  • osteoperosis
  • mass
  • fractures
  • epidemiology
  • determinants
  • association
  • prediction
  • genotypes

Cite this

Estrogen receptor alpha gene polymorphisms and bone mineral density : haplotype analysis in women from the United Kingdom. / Albagha, Omar; McGuigan, Fiona Elizabeth Anne; Reid, David M; Ralston, S.

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

Research output: Contribution to journalArticle

Albagha, Omar ; McGuigan, Fiona Elizabeth Anne ; Reid, David M ; Ralston, S. / Estrogen receptor alpha gene polymorphisms and bone mineral density : haplotype analysis in women from the United Kingdom. In: Journal of Bone and Mineral Research. 2001 ; Vol. 16, No. 1. pp. 128-134.
@article{174fc1bd33fe40d4a1f2ad0aca58754d,
title = "Estrogen receptor alpha gene polymorphisms and bone mineral density: haplotype analysis in women from the United Kingdom",
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 alpha (ER-alpha) 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 Pr 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 Pr haplotype accounting for similar to3{\%} of the variance at both sites. Although the TA repeat polymorphism was in strong linkage disequilibrium (LD) with the PvuII (chi (2) = 109.8; p < 0.0001) and XbaI ((2) = 97.2; p < 0.0001) polymorphisms, there was no overall association between TA repeat number and BMD. We conclude that polymorphisms of the ER- gene are significantly related to BMD) in our population and that this association is dependent on the Pr haplotype, suggesting that it is the Pr haplotype, or a linked polymorphism, that confers risk.",
keywords = "estrogen receptor, bone mineral density, genetic, polymorphism, osteoporosis, postmenopausal women, vitamin-D, osteoperosis, mass, fractures, epidemiology, determinants, association, prediction, genotypes",
author = "Omar Albagha and McGuigan, {Fiona Elizabeth Anne} and Reid, {David M} and S Ralston",
year = "2001",
doi = "10.1359/jbmr.2001.16.1.128",
language = "English",
volume = "16",
pages = "128--134",
journal = "Journal of Bone and Mineral Research",
issn = "0884-0431",
publisher = "WILEY-BLACKWELL",
number = "1",

}

TY - JOUR

T1 - Estrogen receptor alpha gene polymorphisms and bone mineral density

T2 - haplotype analysis in women from the United Kingdom

AU - Albagha, Omar

AU - McGuigan, Fiona Elizabeth Anne

AU - Reid, David M

AU - Ralston, S

PY - 2001

Y1 - 2001

N2 - 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 alpha (ER-alpha) 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 Pr 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 Pr haplotype accounting for similar to3% of the variance at both sites. Although the TA repeat polymorphism was in strong linkage disequilibrium (LD) with the PvuII (chi (2) = 109.8; p < 0.0001) and XbaI ((2) = 97.2; p < 0.0001) polymorphisms, there was no overall association between TA repeat number and BMD. We conclude that polymorphisms of the ER- gene are significantly related to BMD) in our population and that this association is dependent on the Pr haplotype, suggesting that it is the Pr haplotype, or a linked polymorphism, that confers risk.

AB - 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 alpha (ER-alpha) 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 Pr 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 Pr haplotype accounting for similar to3% of the variance at both sites. Although the TA repeat polymorphism was in strong linkage disequilibrium (LD) with the PvuII (chi (2) = 109.8; p < 0.0001) and XbaI ((2) = 97.2; p < 0.0001) polymorphisms, there was no overall association between TA repeat number and BMD. We conclude that polymorphisms of the ER- gene are significantly related to BMD) in our population and that this association is dependent on the Pr haplotype, suggesting that it is the Pr haplotype, or a linked polymorphism, that confers risk.

KW - estrogen receptor

KW - bone mineral density

KW - genetic

KW - polymorphism

KW - osteoporosis

KW - postmenopausal women

KW - vitamin-D

KW - osteoperosis

KW - mass

KW - fractures

KW - epidemiology

KW - determinants

KW - association

KW - prediction

KW - genotypes

U2 - 10.1359/jbmr.2001.16.1.128

DO - 10.1359/jbmr.2001.16.1.128

M3 - Article

VL - 16

SP - 128

EP - 134

JO - Journal of Bone and Mineral Research

JF - Journal of Bone and Mineral Research

SN - 0884-0431

IS - 1

ER -