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Effects of COLIA1 polymorphisms and haplotypes on perimenopausal bone mass, postmenopausal bone loss and fracture risk

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Abstract

Summary

One thousand seven hundred seventeen perimenopausal women from the Danish Osteoporosis Prevention Study were genotyped for the −1997G/T, −1663indelT and +1245G/T polymorphisms in the COLIA1 gen. We found that the −1997T allele and a haplotype containing it were associated with reduced bone mineral density (BMD) and increased bone turnover at menopause and after 10 years of follow-up.

Introduction

We wanted to investigate whether the −1997G/T, −1663indelT and +1245G/T polymorphisms in the COLIA1 gene are associated with perimenopausal bone mass, early postmenopausal bone loss and interact with hormone treatment.

Methods

One thousand seven hundred seventeen perimenopausal women from the Danish Osteoporosis Prevention Study were genotyped, and haplotypes were determined. BMD was examined by dual X-ray absorptiometry.

Results

Women carrying the −1997T variant had lower BMD at all measured sites: lumbar spine BMD 1.030 ± 0.137 g/cm2, 1.016 ± 0.147 g/cm2 and 0.988 ± 0.124 g/cm2 in women with the GG, GT and TT genotypes, respectively (p < 0.05) and total hip BMD 0.921 ± 0.116 g/cm2, 0.904 ± 0.123 g/cm2 and 0.887 ± 0.109 g/cm2 in women with the GG, GT and TT genotypes, respectively (p = 0.01). The effect remained after 10 years although statistical significance was lost. Haplotype 3 (−1997T−1663ins+1245G) was associated with lower bone mass and higher levels of bone turnover. Compared with haplotype 1, haplotype 3 carriers had lower BMD at the lumbar spine, femoral neck and total hip by 0.016 ± 0.007 g/cm2, 0.015 ± 0.006 g/cm2 and 0.017 ± 0.006 g/cm2, respectively (p < 0.05–0.005). No association with postmenopausal changes in bone mass and fracture risk and no overall interaction with the effects of hormone therapy could be demonstrated for any of the polymorphisms in COLIA1.

Conclusions

The −1997G/T polymorphism and haplotype 3 are significantly associated with perimenopausal bone mass, and these effects were sustained up to 10 years after menopause. No association between the −1663indelT or +1245G/T polymorphisms and peri- or postmenopausal bone mass could be demonstrated.

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Acknowledgements

This study was supported by the European Commission (Grant QLK6-CT-2002-02629 (GENOMOS)). We thank Liselotte Stenkjaer and Mette Carstens for skilful technical assistance and DOPS investigators for collaboration.

Conflicts of interest

None of the authors have any conflict of interest related to this study.

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Authors and Affiliations

  1. Department of Endocrinology and Internal Medicine THG, Aarhus University Hospital, Aarhus, Denmark

    N. González-Bofill, L. B. Husted, T. Harsløf, P. Vestergaard & B. L. Langdahl

  2. Department of Endocrinology and Metabolism, Hvidovre University Hospital, Hvidovre, Denmark

    C. L. Tofteng

  3. Department of Endocrinology and Metabolism, Odense Hospital, Odense, Denmark

    B. Abrahamsen

  4. Department of Internal Medicine and Endocrinology, Gentofte Hospital, Gentofte, Denmark

    B. Abrahamsen

  5. Department of Cardiology and Endocrinology, Hillerød Hospital, Hillerød, Denmark

    P. Eiken

  6. Department of Endocrinology and Internal Medicine THG, Aarhus University Hospital, Aarhus, Tage-Hansens Gade 2, 8000, Denmark

    N. González-Bofill

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  1. N. González-Bofill
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  2. L. B. Husted
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  3. T. Harsløf
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  4. C. L. Tofteng
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Correspondence to N. González-Bofill.

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González-Bofill, N., Husted, L.B., Harsløf, T. et al. Effects of COLIA1 polymorphisms and haplotypes on perimenopausal bone mass, postmenopausal bone loss and fracture risk. Osteoporos Int 22, 1145–1156 (2011). https://doi.org/10.1007/s00198-010-1292-4

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