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Identification of novel RANK polymorphisms and their putative association with low BMD among postmenopausal women

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Abstract

Introduction

Bone mineral density (BMD) is the major factor for determining bone strength, which is closely correlated to osteoporotic fracture risk and is largely determined by multiple genetic factors. The RANK (TNFRSF11A), receptor for RANKL, is a member of the tumor necrosis factor receptor (TNFR) superfamily and plays a central role in osteoclast development.

Methods

In order to investigate the effects of RANK polymorphism on BMD and osteoporosis, we directly sequenced the RANK gene in 24 Korean individuals and identified 25 sequence variants. Eleven of these polymorphisms were selected and genotyped in a larger-scale study of postmenopausal women (n = 560). Areal BMD (g/cm2) of the anterior–posterior lumbar spine and the nondominant proximal femur were measured using dual-energy X-ray absorptiometry.

Results

We found that two intronic polymorphisms in the RANK gene [RANK + 34863G > A (rs12458117) and RANK + 35928insdelC (new polymorphism found in this study) in intron 6] were significantly associated with the BMD of the lumbar spine, i.e., rare alleles were significantly associated with low BMD of the lumbar spine among Korean postmenopausal women (p = 0.04 and 0.02, respectively). These polymorphisms were also associated with low BMD of proximal femur sites, including Ward’s triangle, trochanter, and total femur. Our results suggest that +34863G > A and +35928insdelC polymorphisms in RANK are possible genetic factors for low BMD in postmenopausal women.

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Acknowledgements

This study was supported in part by a grant from the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (Project No.: 01-PJ3-PG6-01GN11-0002) and in part by Kyungpook National University Hospital Grant (2003).

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Authors and Affiliations

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

    J.-M. Koh, D. J. Kim & G. S. Kim

  2. Department of Genetic Epidemiology, SNP Genetics, Inc., Rm 1407, 14th floor, Complex B, WooLim Lion’s Valley, 371-28, Gasan-Dong, Geumcheon-Gu, Seoul, 153-803, South Korea

    B. L. Park, H. S. Cheong & H. D. Shin

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

    T.-H. Kim, J.-M. Hong, E. K. Park & S.-Y. Kim

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

    H.-I. Shin & E. K. Park

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

    S.-Y. Kim

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  1. J.-M. Koh
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  2. B. L. Park
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  4. G. S. Kim
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  10. S.-Y. Kim
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  11. H. D. Shin
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Corresponding authors

Correspondence to E. K. Park or S.-Y. Kim.

Electronic supplementary material

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Ad. Table 1

Frequencies of the human RANK gene polymorphisms (DOC 56.5 KB).

Ad. Table 2

Frequencies of the human RANK gene polymorphisms according to the evaluation machines (DOC 47 KB).

Ad. Table 3

Primer sequences for discovery of RNAK polymorphism (DOC 33.5 KB).

Ad. Table 4

Sequences of amplifying and TaqMan probe for RNAK single nucleotide polymorphism (SNP) genotyping (DOC 33 KB).

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Koh, JM., Park, B.L., Kim, D.J. et al. Identification of novel RANK polymorphisms and their putative association with low BMD among postmenopausal women. Osteoporos Int 18, 323–331 (2007). https://doi.org/10.1007/s00198-006-0244-5

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  • DOI: https://doi.org/10.1007/s00198-006-0244-5

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