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Association of TWIST1 gene polymorphisms with bone mineral density in postmenopausal women

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Abstract

Summary

A novel polymorphism (+1871A>G) in the 3′ flanking region and haplotypes were significantly associated with reduced osteoporosis risk and enhanced bone mineral density (BMD). These results suggest that TWIST1 may be a useful genetic marker for osteoporosis. Our results provide preliminary evidence supporting an association of TWIST1 with osteoporosis in postmenopausal women.

Introduction

TWIST1, a basic helix–loop–helix (bHLH) transcription factor, has been implicated in cell lineage determination and differentiation.

Methods

To address the genetic variations in the TWIST1 gene associated with osteoporosis, we investigated the potential involvement of three TWIST1 single-nucleotide polymorphisms (SNPs) in osteoporosis in 729 postmenopausal women. BMD was measured using dual-energy X-ray absorptiometry.

Results

A novel polymorphism in the 3′ flanking region (+1871A>G) was significantly associated with osteoporosis risk (p = 0.007–0.008) and also in multiple comparison (p = 0.02). Consistent with these results, haplotype analysis showed that Block1_ht2 had protective effects in the dominant and additive model (p = 0.006–0.007). Specifically, the +1871A>G polymorphism was overdominantly associated with higher BMD values of the femoral neck (p = 0.039).

Conclusion

These results suggest that TWIST1 may be a useful genetic marker for osteoporosis and may have a role on bone metabolism in humans. Our results provide preliminary evidence supporting an association of TWIST1 with osteoporosis in postmenopausal women.

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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. 091-4845-301-210-13).

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Authors and Affiliations

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

    J.-Y. Hwang, M. J. Go, S. E. Kim, H.-C. Kim, H.-L. Kim & J.-Y. Lee

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

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

  3. Department of Genetic Epidemiology, SNP Genetics, Inc., Room 1407, 14th Floor, B-dong, WooLim Lion’s Valley, 371-28, Gasan-dong, Geumcheon-gu, Seoul, 153-803, Republic of Korea

    H.-D. Shin & B. L. Park

  4. Department of Life Science, Sogang University, 1 Shinsu-dong, Mapogu, Seoul, 121-742, Republic of Korea

    H.-D. Shin

  5. 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

  6. Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Asanbyeongwon-gil 86, Songpa-gu, Seoul, 138-736, Republic of Korea

    S. H. Lee, G. S. Kim & J.-M. Koh

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

    S.-Y. Kim

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  1. J.-Y. Hwang
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  2. S.-Y. Kim
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Correspondence to J.-Y. Lee or J.-M. Koh.

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Joo-Yeon Hwang and Shin-Yoon Kim have equal contributions to this work.

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Hwang, JY., Kim, SY., Lee, S.H. et al. Association of TWIST1 gene polymorphisms with bone mineral density in postmenopausal women. Osteoporos Int 21, 757–764 (2010). https://doi.org/10.1007/s00198-009-1009-8

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  • DOI: https://doi.org/10.1007/s00198-009-1009-8

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