Osteoporosis International

, Volume 18, Issue 3, pp 323–331

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

  • J.-M. Koh
  • B. L. Park
  • D. J. Kim
  • G. S. Kim
  • H. S. Cheong
  • T.-H. Kim
  • J.-M. Hong
  • H.-I. Shin
  • E. K. Park
  • S.-Y. Kim
  • H. D. Shin
Original Article

DOI: 10.1007/s00198-006-0244-5

Cite this article as:
Koh, JM., Park, B.L., Kim, D.J. et al. Osteoporos Int (2007) 18: 323. doi:10.1007/s00198-006-0244-5

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.

Keywords

BMDPolymorphismPostmenopausal womenRANKTNFRSF11A

Supplementary material

198_2006_244_MOESM1_ESM.doc (50 kb)
Ad. Table 1Frequencies of the human RANK gene polymorphisms (DOC 56.5 KB).
198_2006_244_MOESM2_ESM.doc (38 kb)
Ad. Table 2Frequencies of the human RANK gene polymorphisms according to the evaluation machines (DOC 47 KB).
198_2006_244_MOESM3_ESM.doc (26 kb)
Ad. Table 3Primer sequences for discovery of RNAK polymorphism (DOC 33.5 KB).
198_2006_244_MOESM4_ESM.doc (26 kb)
Ad. Table 4Sequences of amplifying and TaqMan probe for RNAK single nucleotide polymorphism (SNP) genotyping (DOC 33 KB).

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2006

Authors and Affiliations

  • J.-M. Koh
    • 1
  • B. L. Park
    • 2
  • D. J. Kim
    • 1
  • G. S. Kim
    • 1
  • H. S. Cheong
    • 2
  • T.-H. Kim
    • 3
  • J.-M. Hong
    • 3
  • H.-I. Shin
    • 4
  • E. K. Park
    • 3
    • 4
  • S.-Y. Kim
    • 3
    • 5
  • H. D. Shin
    • 2
  1. 1.Division of Endocrinology and MetabolismUniversity of Ulsan College of Medicine, Asan Medical CenterSeoulSouth Korea
  2. 2.Department of Genetic EpidemiologySNP Genetics, Inc.SeoulSouth Korea
  3. 3.Skeletal Diseases Genome Research CenterKyungpook National University HospitalDaeguSouth Korea
  4. 4.Department of Pathology and Regenerative Medicine,School of DentistryKyungpook National UniversityDaeguSouth Korea
  5. 5.Department of Orthopedic SurgeryKyungpook National University School of MedicineDaeguSouth Korea