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Estrogen receptor α CA dinucleotide repeat polymorphism is associated with rate of bone loss in perimenopausal women and bone mineral density and risk of osteoporotic fractures in postmenopausal women

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Abstract

Summary

The association between a newly identified CA repeat polymorphism of the estrogen receptor alpha gene (ESR1) with osteoporosis was investigated. Postmenopausal women with <18 CA repeats had low BMD, increased rate of bone loss and increased fracture risk.

Introduction

Studies have shown that intronic dinucleotide repeat polymorphisms in some genes are associated with disease risk by modulating mRNA splicing efficiency. D6S440 is a newly identified intronic CA repeat polymorphism located downstream of the 5’-splicing site of exon 5 of ESR1.

Methods

The associations of D6S440 with bone mineral density (BMD), rate of bone loss and fracture risk were evaluated in 452 pre-, 110 peri- and 622 postmenopausal southern Chinese women using regression models.

Results

Post- but not premenopausal women with less CA repeats had lower spine and hip BMD. The number of CA repeats was linearly related to hip BMD in postmenopausal women (β = 0.008; p = 0.004). Postmenopausal women with CA repeats <18 had higher risks of having osteoporosis (BMD T-score<−2.5 at the spine: OR 2.46, 95% CI 1.30–4.65; at the hip: OR 3.79(1.64–8.74)) and low trauma fractures (OR 2.31(1.29–4.14)) than those with ≥18 repeats. Perimenopausal women with <18 CA repeats had significantly greater bone loss in 18 months at the hip than those with ≥18 repeats (−1.96% vs. −1.61%, p = 0.029).

Conclusions

ESR1 CA repeat polymorphism is associated with BMD variation, rate of bone loss and fracture risk, and this may be a useful genetic marker for fracture risk assessment.

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Acknowledgements

We thank the staff of the Osteoporosis Centre at Queen Mary Hospital and KS Lau for technical support. This project is supported by CRCG Grant, Bone Health Fund, The Matching Grant and The Osteoporosis and Endocrine Research Fund of the University of Hong Kong.

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Authors and Affiliations

  1. Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, China

    B. M. H. Lai, C. L. Cheung & A. W. C. Kung

  2. Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, China

    K. D. K. Luk

Authors
  1. B. M. H. Lai
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  2. C. L. Cheung
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  3. K. D. K. Luk
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  4. A. W. C. Kung
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Corresponding author

Correspondence to A. W. C. Kung.

Additional information

Funding Source: This project is supported by CRCG Grant, Bone Health Fund, Matching Grant and Osteoporosis and Endocrine Research Fund of the University of Hong Kong.

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Lai, B.M.H., Cheung, C.L., Luk, K.D.K. et al. Estrogen receptor α CA dinucleotide repeat polymorphism is associated with rate of bone loss in perimenopausal women and bone mineral density and risk of osteoporotic fractures in postmenopausal women. Osteoporos Int 19, 571–579 (2008). https://doi.org/10.1007/s00198-007-0482-1

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  • DOI: https://doi.org/10.1007/s00198-007-0482-1

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