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Fracture, bone mineral density, and the effects of calcitonin receptor gene in postmenopausal Koreans

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Abstract

Summary

In a candidate gene association study, we found that the variations of calcitonin receptor (CALCR) gene were related to the risk of vertebral fracture and increased bone mineral density (BMD).

Introduction

Calcitonins through calcitonin receptors inhibit osteoclast-mediated bone resorption and modulate calcium ion excretion by the kidney and also prevent vertebral bone loss in early menopause.

Methods

To identify genetically susceptible factors of osteoporosis, we discovered the variations in CALCR gene, genotyped in Korean postmenopausal women (n = 729), and examined the potential involvement of seven single-nucleotide polymorphism (SNPs) and their haplotypes in linkage disequilibrium block (BL_hts).

Results

The SNPs, +43147G > C (intron 7), +60644C > T (exon13, 3' untranslated region), and their haplotypes, BL2_ht1 and BL2_ht2, showed a significant association with risk of vertebral fracture (p = 0.048–0.004) and BL2_ht1 showed a highly significant protective effect. Moreover, the polymorphism +60644C > T showed a highly significant association with BMD at both lumbar spine and femoral neck. The subjects carrying CC and CT genotypes with the SNP, +60644C > T, had higher BMD values at the lumbar spine (p = 0.01–0.001) and femoral neck (p = 0.025–0.009).

Conclusion

These results indicate that the CALCR gene may regulate bone metabolism, and +60644C > T in the CALCR gene may genetically modulate bone phenotype.

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Acknowledgments

This work was supported by intramural grants from the Korea National Institute of Health, the Korea Center for Disease Control of the Republic of Korea (Project No.: 347-6111-211), and a grant from the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (Project No.: 01-PJ3-PG6-01GN11-0002).

Conflict of interest

None.

Author information

Authors and Affiliations

  1. The Center for Genome Science, National Institute of Health, 5 Nokbun-dong, Eunpyung-gu, Seoul, 122-701, Republic of Korea

    H.-J. Lee, J.-Y. Hwang, Y.-J. Kim, B. Jeong, H.-L. Kim & J.-Y. Lee

  2. The Center for Biomedical Sciences, National Institute of Health, 5 Nokbun-dong, Eunpyung-gu, Seoul, 122-701, Republic of Korea

    H.-J. Lee

  3. Skeletal Diseases Genome Research Center, Kyungpook National University Hospital, 44-2, Samduk 2-ga, Jung-gu, Daegu, 700-412, Republic of Korea

    S.-Y. Kim, G. S. Kim, T.-H. Kim, E. K. Park, S. H. Lee & J.-M. Koh

  4. Department of Orthopedic Surgery, Kyungpook National University School of Medicine, 50, Samduk 2-ga, Jung-gu, Daegu, 700-412, Republic of Korea

    S.-Y. Kim

  5. Division of Endocrinology and Metabolism, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 138-736, Republic of Korea

    G. S. Kim, S. H. Lee & J.-M. Koh

  6. Department of Pathology and Regenerative Medicine, School of Dentistry, Kyungpook National University, 188-1, Samduk 2-ga, Jung-gu, Daegu, 700-412, Republic of Korea

    T.-H. Kim & E. K. Park

  7. Nokbun-Dong 5, Eunpyung-Gu, Seoul, 122-701, Republic of Korea

    J.-Y. Lee

Authors
  1. H.-J. Lee
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  2. S.-Y. Kim
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  3. G. S. Kim
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  9. S. H. Lee
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  12. J.-Y. Lee
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Corresponding authors

Correspondence to J.-M. Koh or J.-Y. Lee.

Additional information

H.-J. Lee and S.-Y. Kim contributed equally to this article.

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Lee, HJ., Kim, SY., Kim, G.S. et al. Fracture, bone mineral density, and the effects of calcitonin receptor gene in postmenopausal Koreans. Osteoporos Int 21, 1351–1360 (2010). https://doi.org/10.1007/s00198-009-1106-8

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  • DOI: https://doi.org/10.1007/s00198-009-1106-8

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